1
|
Mazhar A, Hameed A, Ming C, Bhatti SA, Amir M, Khan MU, Muhammad Irfan Manzoor H, Muhammad AH. Development of tolerogenic casein encapsulated quercetin and curcumin nanoparticles to mitigate cow milk allergic responses. Int J Biol Macromol 2025; 314:144396. [PMID: 40398766 DOI: 10.1016/j.ijbiomac.2025.144396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/23/2025] [Accepted: 05/18/2025] [Indexed: 05/23/2025]
Abstract
Casein protein is a primary cause of cow milk allergies (CMA), a major public health concern. This study aimed to develop casein encapsulated quercetin and curcumin nanoparticles (Nps) to modulate CMA and mitigate adverse immunological responses. Nps were synthesized using anti-solvent precipitation method and evaluated for encapsulation efficiency, loading capacity, and functional group interactions. Nps were orally administered to casein-sensitized Albino Wistar rats to evaluate their immunomodulatory potential. The particle size of Nps ranged from 300 to 550 nm. Higher encapsulation efficiency of 79.52 ± 0.334 %, 64.98 ± 0.269 % and loading capacity of 31.81 ± 0.133 %, 25.99 ± 0.107 % were observed for quercetin and curcumin, respectively. The results depicted that Cas-Qur Nps have smallest size than other prepared NPs with irregular morphologies. Prophylactic treatment with Nps significantly suppressed the serum IgE, IL-4, and WBC count in casein sensitized rats. Furthermore, the Nps, especially Cas-Qur-Cur Nps, enhanced the production of IL-10. Histopathological analysis of the intestine revealed reduced inflammation and a prominent brush border surface epithelium in treated groups compared to positive control. The Nps confirmed the immunomodulatory potential by effectively attenuating allergen specific antibodies production, inflammatory cytokines, and neutrophil infiltration in the casein-sensitized rats. These findings highlight their potential as novel therapeutic approach for the management of CMA.
Collapse
Affiliation(s)
- Aimen Mazhar
- College of Food Science and Technology, Zhejiang University of Technology, Huzhou, Zhejiang 310014, People's Republic of China; Department of Human Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Aneela Hameed
- Department of Animal Food Products Technology, Bahauddin Zakariya University, Multan 60800, Pakistan..
| | - Cai Ming
- College of Food Science and Technology, Zhejiang University of Technology, Huzhou, Zhejiang 310014, People's Republic of China.
| | - Sheraz Ahmed Bhatti
- Department of Pathobiology, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Mamoona Amir
- Department of Animal Food Products Technology, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Muhammad Usman Khan
- Department of Food Science and Technology, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Hafiz Muhammad Irfan Manzoor
- Department of Human Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan; Department of Agriculture and Food Technology, Karakoram International University, Gilgit 15100, Pakistan
| | - Ahsan Hafiz Muhammad
- College of Food Science and Technology, Zhejiang University of Technology, Huzhou, Zhejiang 310014, People's Republic of China; Department of Human Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan.
| |
Collapse
|
2
|
Jiang HH, Tang Q, Huang L, Yun X, Shan QW, Chen XQ. Severe upper gastrointestinal hemorrhage due to milk protein allergy: A case report. World J Clin Cases 2025; 13:104039. [PMID: 40385296 PMCID: PMC11752431 DOI: 10.12998/wjcc.v13.i14.104039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 12/21/2024] [Accepted: 01/07/2025] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Upper gastrointestinal hemorrhage is a life-threatening manifestation of cow's milk protein allergy (CMPA). We analyze the clinical characteristics of a case of milk protein allergy manifested as severe upper gastrointestinal hemorrhage. CASE SUMMARY The hospital admitted a 2-month-old male infant due to "melena for 6 days, hematemesis twice". The main symptom was melena, initially occurring once or twice per day, then gradually increasing to five or six times per day at their peak. During the course of the illness, the infant vomited blood, but there were no reports of vomiting, fever, pale complexion, dyspnea, wheezing, or difficulty breathing. Laboratory tests showed hemoglobin level of 87 g/L, platelet count of 349 × 109/L, and eosinophil percentage of 0.031. Coagulation studies were normal. After avoiding certain foods and feeding with an amino acid formula for 2 weeks, a repeat gastroscopy revealed less bleeding. After six weeks, a positive oral food challenge test confirmed a severe CMPA. At the 4-month follow-up, there was no gastrointestinal bleeding, and the infant was growing and developing well. CONCLUSION The manifestations of milk protein allergy are diverse and nonspecific, with gastrointestinal bleeding being less common, especially in infants. When infants present with unexplained massive hematemesis, it's critical to investigate the possibility of CMPA.
Collapse
Affiliation(s)
- Huan-Huan Jiang
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing Tang
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Li Huang
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiang Yun
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing-Wen Shan
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiu-Qi Chen
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
3
|
Bozic M, Roth MS, Martin L, Werder A, Bellutti Enders F. Evaluation of the Cow's Milk and Hen's Egg Ladder in Daily Practice: A Parent Perspective. KLINISCHE PADIATRIE 2025. [PMID: 39832762 DOI: 10.1055/a-2501-5991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Evaluation of the cow's milk (CM) and hen's egg (HE) ladder to improve medical care of children with CM and/or HE allergy. Through an anonymous retrospective online questionnaire, we investigated parent perspectives regarding the therapy option of a CM and HE ladder in children with CM and/or HE allergy. Of the 54 families contacted, 29 took part in the study. 19/29 children had already completed the ladders when the survey took place. 19/29 children showed an allergic reaction during the treatment of whom 17 presented skin rashes. 16/29 parents were anxious to rise to the next step in the protocol. 15/29 had difficulties with the implementation of the therapy due to the child refusing the offered food and organizational issues. Medical support as well as the ladder as a therapy option were scored satisfactory. The participating parents were satisfied with the therapy option and medical care. We identified two main areas for improvement: First, the suggested food for every step should be more diverse, according to the families' culture background and nutritional needs/demands. Second, to reduce anxiety regarding the therapy, parents must be informed that although allergic reactions are common, they remain mild. Furthermore, we will suggest step changes under medical supervision, especially in families with a slow progression of the food ladder. With these improvements, the duration of therapy could be shortened, thus reducing the risk of an allergic reaction, the need for medical care by an allergist and therefore reducing healthcare costs.
Collapse
Affiliation(s)
- Manuela Bozic
- Allergy and Clinical Immunology, University Children's Hospital Basel, Basel, Switzerland
| | - Michèle S Roth
- Allergy and Clinical Immunology, University Children's Hospital Basel, Basel, Switzerland
| | - Lina Martin
- Nutrional Health, University Children's Hospital Basel, Basel, BS, CH, Basel, Switzerland
| | - Andrea Werder
- Nutrional Health, University Children's Hospital Basel, Basel, BS, CH, Basel, Switzerland
| | - Felicitas Bellutti Enders
- Allergy and Clinical Immunology, University Children's Hospital Basel, Basel, BS, CH, Basel, Switzerland
| |
Collapse
|
4
|
Çeliksoy MH, Naiboglu S, Topal E, Karadağ ŞİK, Yılmaz E, Bologur H. The effect of formula type on the prognosis of allergic proctocolitis due to cow's milk allergy. Allergol Immunopathol (Madr) 2025; 53:126-130. [PMID: 39786885 DOI: 10.15586/aei.v53i1.1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 11/12/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Food protein-induced allergic proctocolitis is a nonimmunoglobulin E-mediated, self-limited food allergy of the rectum and the colon. Cow's milk protein is the most common allergen responsible for the disease. OBJECTIVE This study aimed to investigate the roles of different types of formulas in building early tolerance to food protein-induced allergic proctocolitis in infants. METHODS The medical records of 45 pediatric patients diagnosed with proctocolitis due to cow's milk allergy between August 2021 and August 2023 and whose disease progression was followed in three tertiary care centers were reviewed retrospectively. RESULTS The study included 45 patients who were diagnosed with proctocolitis due to cow's milk allergy (24 males, 21 females; median age: 4 months). Among them, 24 patients were fed an amino acid-based formula, and 21 (46.7%) patients were fed an extensively hydrolyzed formula. The average age of acquisition of cow's milk tolerance was lower in the group fed with the amino acid-based formula than in the group fed with extensively hydrolyzed formula (P = 0.038). Furthermore, the group fed with amino acid-based formula had a shorter tolerance period than the group fed with the extensively hydrolyzed formula group (P = 0.044). CONCLUSION Compared to an extensively hydrolyzed formula, an amino acid-based formula led to the early development of tolerance in children with allergic proctocolitis induced by cow's milk.
Collapse
Affiliation(s)
- Mehmet Halil Çeliksoy
- Department of Pediatric Allergy and Immunology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul, Turkey;
| | - Sezin Naiboglu
- Department of Pediatric Allergy and Immunology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul, Turkey
| | - Erdem Topal
- Medical Faculty, Pediatric Allergy and Immunology, Inonu University, Malatya, Turkey
| | - Şefika İlknur Kökçü Karadağ
- Department of Pediatric Allergy and Immunology, Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ercan Yılmaz
- Medical Faculty, Pediatric Allergy and Immunology, Inonu University, Malatya, Turkey
| | - Hamit Bologur
- Department of Pediatric Allergy and Immunology, Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, Turkey
| |
Collapse
|
5
|
Li H, Yang L, Li J, Gao Q, Liu T, Zou Y, Chen X, Li H, Yu J. Allergenicity evaluation of an extensively hydrolyzed infant formula based on cow milk protein. Food Funct 2024; 15:11036-11046. [PMID: 39431858 DOI: 10.1039/d4fo03582h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2024]
Abstract
Cow milk protein allergy (CMPA) is the most common food allergy in infants. Currently, hypoallergenic infant formulas on the market are mainly divided into extensively hydrolyzed whey protein formulas and extensively hydrolyzed casein formulas. There are few extensively hydrolyzed infant formulas (EHFs) with a similar protein composition to breast milk. Therefore, we developed a hypoallergenic infant formula based on extensively hydrolyzed cow milk protein (whey protein-to-casein ratio of 6 : 4) and evaluated its allergenicity in vitro and in vivo. The results showed that the antigenicity of EHF was significantly decreased. The levels of Treg and Th1 cells were increased, while the levels of Th2 cells, IgE and IgG1, plasma histamine and serum mast cell enzymes were significantly decreased. At the same time, the allergic symptoms of the jejunum and lungs of mice were relieved. This study provides a solution for the development of cow milk protein based hypoallergenic infant formulas.
Collapse
Affiliation(s)
- Hongbo Li
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Lin Yang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Jiayi Li
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Quan Gao
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Tiantian Liu
- School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China
| | - Yang Zou
- Tianjin Haihe Dairy Co., Ltd, No. 158, Jingwu Road, Tianjin Airport Economic Zone, Tianjin Economic-Technological Development Area (TEDA), Tianjin, 300457, China
| | - Xiaohong Chen
- Tianjin Haihe Dairy Co., Ltd, No. 158, Jingwu Road, Tianjin Airport Economic Zone, Tianjin Economic-Technological Development Area (TEDA), Tianjin, 300457, China
| | - Hongjuan Li
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Jinghua Yu
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
| |
Collapse
|
6
|
Ge X, Qu X, Xie C, Zang J, Wu W, Lv L. The influence on the structure and allergenicity of milk β-lactoglobulin by methylglyoxal during thermal processing. Food Res Int 2024; 196:115043. [PMID: 39614482 DOI: 10.1016/j.foodres.2024.115043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 08/04/2024] [Accepted: 09/01/2024] [Indexed: 12/01/2024]
Abstract
This study aims to investigate the effects of the typical glycation intermediate methylglyoxal (MGO) on the structure and allergenicity of milk β-lactoglobulin (βLG) during thermal processing. Structural changes were assessed using SDS-PAGE, intrinsic fluorescence, circular dichroism, and HPLC-MS/MS. Allergenicity was evaluated through in vitro and in vivo experiments. The conformational changes of βLG significantly were induced by MGO during heat treatment, with a 41.3% decrease in α-helix content and a 25.4% increase in random structure. Furthermore, the lysine, arginine, aspartic acid, and histidine residues in βLG were modified by MGO, which may disrupt or mask allergenic epitopes. Additionally, MGO treatment resulted in a reduction of 41.1% and 26.8% in the pro-inflammatory mediators histamine and β-hexosaminidase in KU812 cells, respectively. Additionally, cytokine levels of IL-4 and IL-13 were reduced by 26.3% and 21.75%, respectively. In mouse experiments, compared to the βLG group, the MGO-βLG group showed a 2-4 fold decrease in IgE, IgG, and IgG1 levels. After reacting with βLG, MGO can reduce serum histamine release by up to 73.9% and mast cell protease-1 (MCP-1) release by 40.8%. These results indicate that the typical glycation intermediate MGO can modify the allergenic epitopes of milk βLG during thermal processing, thereby affecting its allergenicity. This study provides a reference for elucidating the natural rules of allergenicity changes during milk thermal processing.
Collapse
Affiliation(s)
- Xinyu Ge
- College of Food Science and Engineering, Qingdao Agricultural University,Qingdao 266109, China
| | - Xin Qu
- Qingdao Municipal Center for Disease Control and Prevention, 175 Shandong Road, Shibei District, Qingdao, Shandong Province 266033, China
| | - Chunxia Xie
- Clinical Laboratory, Qingdao Central Hospital, China
| | - Jinhong Zang
- College of Food Science and Engineering, Qingdao Agricultural University,Qingdao 266109, China
| | - Wei Wu
- College of Food Science and Engineering, Qingdao Agricultural University,Qingdao 266109, China; Academy of Dongying Efficient Agricultural Technology and Industry on Saline and Alkaline Land in Collaboration with Qingdao Agricultural University, China; Qingdao Institute of Special Food, Qingdao 266109, China.
| | - Liangtao Lv
- College of Food Science and Engineering, Qingdao Agricultural University,Qingdao 266109, China; Qingdao Institute of Special Food, Qingdao 266109, China.
| |
Collapse
|
7
|
Castro AM, Navarro S, Carvajal I, García A, Suárez M, Toyos P, Rodríguez S, Jimenez S, González D, Molinos C, Pérez-Solís D, Fernández P, Margolles A, Díaz-Martín JJ, Gutiérrez-Díaz I, Delgado S. Evolutive Study of Dietary Aspects and Intestinal Microbiota of Pediatric Cohort with Cow's Milk Protein Allergy. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1113. [PMID: 39334645 PMCID: PMC11429558 DOI: 10.3390/children11091113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 09/05/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024]
Abstract
BACKGROUND One of the most common food allergies in the pediatric population is allergy to cow's milk protein (CMPA). Treatment consists of avoiding cow's milk proteins in lactating mothers and/or using therapeutic formulas based on hydrolysates or vegetable formulas. In infants with CMPA at diagnosis, a different gut microbial profile has been found compared to healthy children, with a reduction in beneficial bacteria. The aim of this study was to evaluate changes in the gut microbiota profile and its metabolites, dietary patterns and anthropometric variables in a pediatric cohort with CMPA after six months on a restrictive diet compared to healthy controls. METHODS In total, 21 patients diagnosed with CMPA and a control group of 24 healthy infants participated in this study. The fecal microbiota of all participants were investigated by metataxonomic analysis of 16S rDNA amplicons, and fecal short-chain fatty acids were measured by gas chromatography. Epidemiological assessment and dietary questionnaires were carried out for both groups. RESULTS Regarding growth, no significant differences were found, but differences in dietary intake of some macro- and micronutrients were observed. Patients who were breastfed at six months had higher bifidobacteria and lipid intakes than patients fed with hydrolyzed formulas. CONCLUSIONS Although the growth of CMPA infants fed with therapeutic formula is similar to breastfed CMPA infants, there are differences in microbiota composition and macronutrient intake that underline the importance of continued breastfeeding in CMPA cases.
Collapse
Affiliation(s)
- Ana M. Castro
- Grupo MicroHealth, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Asturias, Spain; (A.M.C.); (A.M.); (I.G.-D.); (S.D.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Asturias, Spain
| | - Sandra Navarro
- Pediatría, CAP Teatinos-Corredoria, 33011 Oviedo, Asturias, Spain;
| | | | - Agueda García
- Pediatría, CAP Vallobin-La Florida, 33012 Oviedo, Asturias, Spain;
| | - Marta Suárez
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - Paula Toyos
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - Silvia Rodríguez
- Pediatría, Hospital Universitario de San Agustín, 33401 Avilés, Asturias, Spain; (S.R.); (D.P.-S.)
| | - Santiago Jimenez
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - David González
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - Cristina Molinos
- Pediatría, Hospital Universitario de Cabueñes, 33394 Gijón, Asturias, Spain;
| | - David Pérez-Solís
- Pediatría, Hospital Universitario de San Agustín, 33401 Avilés, Asturias, Spain; (S.R.); (D.P.-S.)
| | - Porifirio Fernández
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - Abelardo Margolles
- Grupo MicroHealth, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Asturias, Spain; (A.M.C.); (A.M.); (I.G.-D.); (S.D.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Asturias, Spain
| | - Juan J. Díaz-Martín
- Pediatría, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Asturias, Spain; (M.S.); (P.T.); (D.G.)
| | - Isabel Gutiérrez-Díaz
- Grupo MicroHealth, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Asturias, Spain; (A.M.C.); (A.M.); (I.G.-D.); (S.D.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Asturias, Spain
| | - Susana Delgado
- Grupo MicroHealth, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Asturias, Spain; (A.M.C.); (A.M.); (I.G.-D.); (S.D.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Asturias, Spain
| |
Collapse
|
8
|
Gelsomino M, Liotti L, Barni S, Mori F, Giovannini M, Mastrorilli C, Pecoraro L, Saretta F, Castagnoli R, Arasi S, Klain A, del Giudice MM, Novembre E. Elimination Diets in Lactating Mothers of Infants with Food Allergy. Nutrients 2024; 16:2317. [PMID: 39064760 PMCID: PMC11279873 DOI: 10.3390/nu16142317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 07/10/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Breastfeeding is the most important nutrition source for infants. However, managing breastfed infants with signs and symptoms related to food allergy can be difficult. Many studies have shown the presence of different food allergens in breast milk, but the clinical role of these antigens in human milk is still much debated. Milk is the main suspect in exclusively breastfed infants with signs and symptoms attributable to food allergy, even if other foods may be responsible. This narrative review analyzes the recommendations provided by international guidelines to determine the diagnosis and management of IgE-mediated and non-IgE-mediated food allergies in exclusively breastfed infants. Dietary restrictions in lactating mothers of infants with suspected FA are usually not necessary. Only in the very few cases where significant allergy signs and symptoms occur in the infant during exclusive breastfeeding should the lactating mother follow an elimination diet for the suspected food for a short period.
Collapse
Affiliation(s)
- Mariannita Gelsomino
- Pediatric Allergy Unit, Department of Life Sciences and Public Health, University Foundation Policlinico Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Lucia Liotti
- Pediatric Unit, Department of Mother and Child Health, Salesi Children’s Hospital, 60123 Ancona, Italy;
| | - Simona Barni
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
| | - Francesca Mori
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
| | - Mattia Giovannini
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.)
- Department of Health Sciences, University of Florence, 50139 Florence, Italy;
| | - Carla Mastrorilli
- Pediatric Hospital Giovanni XXIII, Pediatric and Emergency Department, AOU Policlinic of Bari, 70126 Bari, Italy;
| | - Luca Pecoraro
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37126 Verona, Italy;
| | - Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Riccardo Castagnoli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefania Arasi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Angela Klain
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Michele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Elio Novembre
- Department of Health Sciences, University of Florence, 50139 Florence, Italy;
| |
Collapse
|
9
|
Fakih-Botero I, Cerchiaro-Mejia MC, Rusinque MJ, Palacios-Ariza MA, Plata-Garcia CE, Peña-Hernández S. Out-of-pocket expenses and parent reported quality of life in children with cow's milk protein allergy in Bogotá, Colombia. J Pediatr Gastroenterol Nutr 2024; 79:18-25. [PMID: 38587147 DOI: 10.1002/jpn3.12203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 02/10/2024] [Accepted: 03/11/2024] [Indexed: 04/09/2024]
Abstract
OBJECTIVE To identify the out-of-pocket expenses and parent-reported quality of life (QoL) of children with a diagnosis of cow's milk protein allergy between the ages of 0 and 5 using the Food Allergy Quality of Life Questionnaire - Parent Form. METHODS A cross-sectional study was conducted in two tertiary care centers in Bogotá. Demographic, medical information, and QoL scores were collected by parental interview. We carried out a cost-of-illness analysis based on self-reported out-of-pocket expenses attributed to the treatment as a whole and the family's monthly income. Exploratory analyses used the QoL scores and the percentage of out-of-pocket expenses attributable to treatment as outcomes. RESULTS 122 families were analyzed. Median subject age was 17 months (Q1-Q3: 11-26.75 months) and female subjects made up 71% of the sample. The median QoL score was 3.21 points (Q1-Q3: 2.43-4.34) and only differed by age groups and personal history of other food allergies. The median out-of-pocket treatment related costs was 300,000 Colombian pesos (COP) (Q1-Q3: 280,000-340,000 COP). About 17% of the families had to pay over 15% of their monthly income to purchase food and dietary products. Out-of-pocket treatment related costs differed depending on whether the treatment included formulas (Mann-Whitney test p < 0.001). Out-of-pocket treatment expenses were uncorrelated with the QoL scores. CONCLUSION Food allergy related QoL scores were not associated with out-of-pocket expenses as a whole or as a fraction of monthly income but were higher in children with additional food allergies and in older age groups, suggesting a lower QoL.
Collapse
Affiliation(s)
- Isabella Fakih-Botero
- Pediatric Residency Program, Facultad de Medicina, Fundación Universitaria Sanitas, Bogotá, Colombia
| | | | - Maria Juliana Rusinque
- Pediatric Residency Program, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | | | | | - Stephania Peña-Hernández
- Departamento de Gastroenterología, Fundación Cardioinfantil - Instituto de Cardiología, Bogotá, Colombia
| |
Collapse
|
10
|
Oliveros LV, Brown JM, Fabbrini AL, Farrar AA, Lamos L, Florio J, Beacker J, Baran JV, Wilsey MJ. Managing cow's milk protein allergy during the 2022 formula shortage: decision-making among pediatric healthcare providers. FRONTIERS IN ALLERGY 2024; 5:1359103. [PMID: 38841604 PMCID: PMC11150790 DOI: 10.3389/falgy.2024.1359103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 04/30/2024] [Indexed: 06/07/2024] Open
Abstract
Introduction Cow's milk protein allergy (CMPA) affects 2%-7% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding healthcare providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. Methods This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. Results 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Discussion Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care.
Collapse
Affiliation(s)
- Lea V. Oliveros
- Office of Medical Education, Alabama College of Osteopathic Medicine, Dothan, AL, United States
| | - Jerry M. Brown
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Abigail L. Fabbrini
- Office of Medical Education, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States
| | - Andrew A. Farrar
- Office of Medical Education, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States
| | - Luke Lamos
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Jared Florio
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Jesse Beacker
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Jessica V. Baran
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Michael J. Wilsey
- Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, FL, United States
| |
Collapse
|
11
|
Kuang X, Deng Z, Feng B, He R, Chen L, Liang G. The mechanism of epigallocatechin-3-gallate inhibiting the antigenicity of β-lactoglobulin under pH 6.2, 7.4 and 8.2: Multi-spectroscopy and molecular simulation methods. Int J Biol Macromol 2024; 268:131773. [PMID: 38657930 DOI: 10.1016/j.ijbiomac.2024.131773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/01/2024] [Accepted: 04/21/2024] [Indexed: 04/26/2024]
Abstract
The antigenicity of β-lactoglobulin (β-LG) can be influenced by pH values and reduced by epigallocatechin-3-gallate (EGCG). However, a detailed mechanism concerning EGCG decreasing the antigenicity of β-LG at different pH levels lacks clarity. Here, we explore the inhibition mechanism of EGCG on the antigenicity of β-LG at pH 6.2, 7.4 and 8.2 using enzyme-linked immunosorbent assay, multi-spectroscopy, mass spectrometry and molecular simulations. The results of Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) elucidate that the noncovalent binding of EGCG with β-LG induces variations in the secondary structure and conformations of β-LG. Moreover, EGCG inhibits the antigenicity of β-LG the most at pH 7.4 (98.30 %), followed by pH 6.2 (73.18 %) and pH 8.2 (36.24 %). The inhibitory difference is attributed to the disparity in the number of epitopes involved in the interacting regions of EGCG and β-LG. Our findings suggest that manipulating pH conditions may enhance the effectiveness of antigenic inhibitors, with the potential for further application in the food industry.
Collapse
Affiliation(s)
- Xiaoyu Kuang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China
| | - Zhifen Deng
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China
| | - Bowen Feng
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China
| | - Ran He
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China
| | - Lang Chen
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China
| | - Guizhao Liang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400045, China.
| |
Collapse
|
12
|
Castro AM, Gutiérrez-Díaz I, Saiz ML, Navarro S, Suárez M, Carbajal I, García Á, Sariego L, Toyos P, Rodríguez S, Jiménez S, González D, Molinos C, Pérez D, Fernández P, Suárez-Alvarez B, Margolles A, Díaz JJ, Delgado S. Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis. J Pediatr Gastroenterol Nutr 2024; 78:836-845. [PMID: 38344848 DOI: 10.1002/jpn3.12155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 01/12/2024] [Accepted: 01/24/2024] [Indexed: 03/08/2024]
Abstract
OBJECTIVE Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.
Collapse
Affiliation(s)
- Ana M Castro
- MicroHealth Group, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC)/Instituto Biosanitario del Principado de Asturias (ISPA), Villaviciosa, Asturias, Spain
| | - Isabel Gutiérrez-Díaz
- MicroHealth Group, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC)/Instituto Biosanitario del Principado de Asturias (ISPA), Villaviciosa, Asturias, Spain
| | - María L Saiz
- Translational Immunology, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Sandra Navarro
- Primary Care Center Teatinos-Corredoria, Oviedo, Asturias, Spain
| | | | | | - Águeda García
- Primary Care Center Vallobin-La Florida, Oviedo, Asturias, Spain
| | - Lydia Sariego
- MicroHealth Group, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC)/Instituto Biosanitario del Principado de Asturias (ISPA), Villaviciosa, Asturias, Spain
| | - Paula Toyos
- Pediatric Group, ISPA, Oviedo, Asturias, Spain
| | - Silvia Rodríguez
- Pediatrics Service, Hospital Universitario de San Agustín, Avilés, Asturias, Spain
| | | | | | - Cristina Molinos
- Pediatrics Department, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain
| | - David Pérez
- Pediatrics Service, Hospital Universitario de San Agustín, Avilés, Asturias, Spain
| | | | - Beatriz Suárez-Alvarez
- Translational Immunology, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Abelardo Margolles
- MicroHealth Group, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC)/Instituto Biosanitario del Principado de Asturias (ISPA), Villaviciosa, Asturias, Spain
| | - Juan J Díaz
- Pediatric Group, ISPA, Oviedo, Asturias, Spain
| | - Susana Delgado
- MicroHealth Group, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC)/Instituto Biosanitario del Principado de Asturias (ISPA), Villaviciosa, Asturias, Spain
| |
Collapse
|
13
|
Zhao L, Gao P, Zhang Y, Wang X, Lu S, Yue C, Bai C, Wu W, Zhang Y, Zhao Z. Measurement of degree of hydrolysis and molecular weight distribution of protein hydrolysates by liquid chromatography-mass spectrometry. Talanta 2024; 268:125347. [PMID: 37913595 DOI: 10.1016/j.talanta.2023.125347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/03/2023]
Abstract
Enzymatic hydrolysis of milk protein is an effective way to improve protein digestibility, to reduce their allergenicity and to produce peptides with better functionalities. Among the process, the degree of hydrolysis (DH) and molecular weight distribution (MWD) of protein hydrolysates are two important parameters that need to be monitored. In this work, a new method based on liquid chromatography-mass spectrometry (LC-MS) was developed for the first time to accurately detect the DH and the MWD of proteolytic peptides. With LC-MS, the content of free amine groups released during hydrolysis was acquired by direct analysis of free trinitrobenzene sulfonic acid (TNBS) for DH assay, overcoming the disadvantage of TNBS-based spectral method. Based on this method, the DH% values of five protein hydrolysis samples were determined and consistent with file specification values. Compared to the size-exclusion high-performance liquid chromatography (SE-HPLC) method, LC-MS was capable of measuring MWD (similar results with file specification values) while additionally providing precise molecular weight and amino acid sequence information for each proteolytic peptide. This method was characterized by its simplicity, accuracy, and reproducibility, making it a valuable technology for monitoring proteolysis and producing peptides with better functionality.
Collapse
Affiliation(s)
- Lingyu Zhao
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Peng Gao
- Heilongjiang Feihe Dairy Co., Ltd, Beijing, 100016, China.
| | - Yuanyuan Zhang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiangxin Wang
- Heilongjiang Feihe Dairy Co., Ltd, Beijing, 100016, China
| | - Siyu Lu
- Heilongjiang Feihe Dairy Co., Ltd, Beijing, 100016, China
| | - Chunlin Yue
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Chengling Bai
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Wenjing Wu
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yangyang Zhang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhenwen Zhao
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China.
| |
Collapse
|
14
|
Fabbrini AL, Farrar AA, Brown JM, Oliveros LV, Florio J, Beacker J, Lamos L, Baran JV, Wilsey MJ. Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage. FRONTIERS IN ALLERGY 2024; 4:1333570. [PMID: 38260176 PMCID: PMC10801258 DOI: 10.3389/falgy.2023.1333570] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 12/21/2023] [Indexed: 01/24/2024] Open
Abstract
The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.
Collapse
Affiliation(s)
- Abigail L. Fabbrini
- Office of Medical Education, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States
| | - Andrew A. Farrar
- Office of Medical Education, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States
| | - Jerry M. Brown
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Lea V. Oliveros
- Office of Medical Education, Alabama College of Osteopathic Medicine, Dothan, AL, United States
| | - Jared Florio
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Jesse Beacker
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Luke Lamos
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Jessica V. Baran
- Office of Medical Education, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, United States
| | - Michael J. Wilsey
- Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, FL, United States
| |
Collapse
|
15
|
Alfonso RMJ, Rubí IAK, Manuel TME, Roberto CB, Alejandra RCM, de Jesús MVI, Gabriela AGA, Vladimir BND, Lucía CG, Antonio CBJ, Sergio DM, Esther FFL, Manuel Enrique GPM, Ileana GCJ, Elena HHR, Elena LRA, Héctor MA, Carlos MN, José Antonio OM, Iván OGC, Rubén PV, Nicolás RMJ, Del Mar SDOGM, Gerardo SM, Eugenia URM, Liliana WD, Hideo WKG, Yvan V. Mexican consensus on cow's milk protein allergy. Allergol Immunopathol (Madr) 2024; 52:24-37. [PMID: 38186191 DOI: 10.15586/aei.v52i1.958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/04/2023] [Indexed: 01/09/2024]
Abstract
BACKGROUND The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Casas Guzik Lucía
- Pediatric Gastroenterology, Hospital Infantil de Morelia Eva Sámano de López Mateos, Morelia, México
| | | | | | | | | | | | | | | | | | - Méndez Nieto Carlos
- Pediatric Gastroenterology, Hospital Infantil de Especialidades, Ciudad Juárez, Mexico
| | | | | | - Peña Vélez Rubén
- Pediatric Gastroenterology, Hospital General de Puebla Dr. Eduardo Vázquez N., Puebla, Mexico
| | | | | | | | | | | | | | - Vandenplas Yvan
- Pediatric Gastroenterology, KidZ Health Castle, UZ Brussel; Vrije Universiteit Brussel, Brussels, Belgium
| |
Collapse
|
16
|
Kocic M, Rasic P, Marusic V, Prokic D, Savic D, Milickovic M, Kitic I, Mijovic T, Sarajlija A. Age-specific causes of upper gastrointestinal bleeding in children. World J Gastroenterol 2023; 29:6095-6110. [PMID: 38186684 PMCID: PMC10768410 DOI: 10.3748/wjg.v29.i47.6095] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 11/05/2023] [Accepted: 12/01/2023] [Indexed: 12/19/2023] Open
Abstract
The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.
Collapse
Affiliation(s)
- Marija Kocic
- Department of Gastroenterology, Hepatology and Nutrition, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
| | - Petar Rasic
- Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
| | - Vuk Marusic
- Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Dragan Prokic
- Department of Gastroenterology, Hepatology and Nutrition, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Djordje Savic
- Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Maja Milickovic
- Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Ivana Kitic
- Department of Gastroenterology, Hepatology and Nutrition, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Tanja Mijovic
- Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
| | - Adrijan Sarajlija
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
- Pediatric Day Care Hospital Department, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, Belgrade 11000, Serbia
- Faculty of Medicine, University of Eastern Sarajevo, Foča 73300, Bosnia and Herzegovina
| |
Collapse
|
17
|
Canziani KE, Ruiz MC, Candia MR, Ilid M, Feregotti E, Curciarello R, Álvarez MC, Guzmán L, Bernedo V, García M, Bohle B, Docena GH, Muglia CI. Food-sensitized pediatric patients show colonic cow's milk protein-specific Th2 cells. J Leukoc Biol 2023; 114:434-442. [PMID: 37478370 DOI: 10.1093/jleuko/qiad083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 06/21/2023] [Accepted: 07/07/2023] [Indexed: 07/23/2023] Open
Abstract
Food allergies have become a health concern worldwide. Around 6% to 10% of children are allergic to cow's milk proteins. We have previously characterized colorectal polyps in patients sensitized to food allergens. These polyps are classified as inflammatory and present a type 2 environment, with elevated interleukin (IL)-13 and IL-4, and are a site of immunoglobulin E synthesis. In this study, we characterized and isolated cow's milk protein-specific T cell lines and T cell clones from the lamina propria of polyps from patients sensitized to these proteins. Isolated T cells responded to cow's milk proteins similarly to peripheral blood T cells, showing antigen-specific cell proliferation and Th2 cytokines release in vitro. T cell clones obtained were all CD4+ T cells and expressed the membrane TCRαβ receptor and secreted higher IL-4, IL-5, and IL-13 amounts than unstimulated cells, whereas interferon γ secretion remained unchanged. Remarkably, the gut homing chemokine receptor CCR9 was augmented in cow's milk-specific peripheral and lamina propria T cells, and CCL25 was found to be expressed in the inflammatory polyp tissue and not in the adjacent mucosa. In conclusion, we isolated and characterized cow's milk-specific lamina propria CD4+ Th2 cells from colonic inflammatory polyps. CCR9 expression on these cells, along with increase secretion of CCL25 in the polyp, favors recruitment and cow's milk-specific allergic response within the inflammatory polyp tissue. Our findings may be critical to understand the underlying mechanism that promotes immunoglobulin E synthesis in the colon of cow's milk proteins allergic patients, contributing to the development of novel T cell-targeted immunotherapies.
Collapse
Affiliation(s)
- Karina E Canziani
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - María Carolina Ruiz
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Martín R Candia
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Manuela Ilid
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Emanuel Feregotti
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Renata Curciarello
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - María Cecilia Álvarez
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Luciana Guzmán
- Servicio de Gastroenterología, Hospital de Niños Sor María Ludovica, La Plata, Calle 14 N°1631, 1900, La Plata, Argentina
| | - Viviana Bernedo
- Servicio de Gastroenterología, Hospital de Niños Sor María Ludovica, La Plata, Calle 14 N°1631, 1900, La Plata, Argentina
| | - Marcela García
- Sala de Alergia, Hospital de Niños Sor María Ludovica, Calle 14 N°1631, 1900, La Plata, Argentina
| | - Barbara Bohle
- Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria
| | - Guillermo Horacio Docena
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| | - Cecilia Isabel Muglia
- Instituto de Estudios Inmunológicos y Fisiopatológicos, CONICET - Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, asociado Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Boulevard 120 N°1489, 1900, La Plata, Argentina
| |
Collapse
|
18
|
Florquin M, Eerdekens A. What is Known About Cow's Milk Protein Allergy in Preterm Infants? Breastfeed Med 2023; 18:767-778. [PMID: 37856666 DOI: 10.1089/bfm.2023.0122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2023]
Abstract
Background: Cow's milk protein allergy (CMPA) is well described in term infants, as opposed to preterm infants. In preterm infants, CMPA shares many gastrointestinal symptoms with necrotizing enterocolitis (NEC). Objectives: To evaluate the presentation of CMPA in preterm infants and to investigate the different diagnostic and therapeutic options. Materials and Methods: We searched for the relevant literature using the medical databases PubMed, Web of Science, and the Cochrane Library. We performed a post hoc analysis on the 25 case reports included in this study. Results: Literature was scarce and heterogeneous. The majority of preterm infants with CMPA were exposed to bovine-based milk proteins before the development of symptoms. The most common clinical manifestations were bloody stools, vomiting, and abdominal distension. Of the 25 cases, only 7 (28%) retained human milk in their diet after diagnosis. In the larger studies, no study has human milk as primary feeding choice after diagnosis. Conclusions: Preterm infants exposed to a type of cow's milk-based formula in their first days of life have a higher risk of developing CMPA. Most of the preterm infants are no longer fed with human milk after the diagnosis of CMPA is made, which is in contrast with current nutrition guidelines in preterm infants. We strongly advocate that human milk with mothers on a cow's milk-free diet is the first choice of feed after the diagnosis of CMPA. Prospective studies are necessary to obtain more information regarding clinical presentation, diagnostic tools, and therapeutic approaches.
Collapse
Affiliation(s)
- Mona Florquin
- Department of Pediatrics and University Hospital Leuven, KU Leuven, Belgium
| | - An Eerdekens
- Department of Neonatology, University Hospital Leuven, KU Leuven, Belgium
| |
Collapse
|
19
|
Xu Y, Ahmed I, Zhao Z, Lv L. A comprehensive review on glycation and its potential application to reduce food allergenicity. Crit Rev Food Sci Nutr 2023; 64:12184-12206. [PMID: 37683268 DOI: 10.1080/10408398.2023.2248510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2023]
Abstract
Food allergens are a major concern for individuals who are susceptible to food allergies and may experience various health issues due to allergens in their food. Most allergenic foods are subjected to heat treatment before being consumed. However, thermal processing and prolonged storage can cause glycation reactions to occur in food. The glycation reaction is a common processing method requiring no special chemicals or equipment. It may affect the allergenicity of proteins by altering the structure of the epitope, revealing hidden epitopes, concealing linear epitopes, or creating new ones. Changes in food allergenicity following glycation processing depend on several factors, including the allergen's characteristics, processing parameters, and matrix, and are therefore hard to predict. This review examines how glycation reactions affect the allergenicity of different allergen groups in allergenic foods.
Collapse
Affiliation(s)
- Yue Xu
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
| | - Ishfaq Ahmed
- Haide College, Ocean University of China, Qingdao, China
| | - Zhengxi Zhao
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
| | - Liangtao Lv
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
| |
Collapse
|
20
|
Bringheli I, Brindisi G, Morelli R, Marchetti L, Cela L, Gravina A, Pastore F, Semeraro A, Cinicola B, Capponi M, Gori A, Pignataro E, Piccioni MG, Zicari AM, Anania C. Kiwifruit's Allergy in Children: What Do We Know? Nutrients 2023; 15:3030. [PMID: 37447357 DOI: 10.3390/nu15133030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 06/28/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Kiwifruit allergy is an emerging pathological condition in both general and pediatric populations with a wide range of symptoms linked to variable molecular patterns, justifying systemic and cross-reactions with other allergens (i.e., latex, pollen, and fruit). Skin prick test (SPT), specific serum IgE (Act d 1, Act d 2, Act d 5, Act d 8, and Act d 10) directed against five out of thirteen molecular allergens described in the literature, and oral test challenge with kiwifruit are available for defining diagnosis. The management is similar to that of other food allergies, mostly based on an elimination diet. Although kiwi allergy has been on the rise in recent years, few studies have evaluated the clinical characteristics and methods of investigating this form of allergy. Data collected so far show severe allergic reaction to be more frequent in children compared to adults. Therefore, the aim of this review is to collect the reported clinical features and the available association with specific molecular patterns of recognition to better understand how to manage these patients and improve daily clinical practice.
Collapse
Affiliation(s)
- Ivana Bringheli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Giulia Brindisi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Rebecca Morelli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Lavinia Marchetti
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Ludovica Cela
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandro Gravina
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesca Pastore
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Antonio Semeraro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Bianca Cinicola
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Martina Capponi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandra Gori
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Elia Pignataro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Maria Grazia Piccioni
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Anna Maria Zicari
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Caterina Anania
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| |
Collapse
|
21
|
Cela L, Brindisi G, Gravina A, Pastore F, Semeraro A, Bringheli I, Marchetti L, Morelli R, Cinicola B, Capponi M, Gori A, Pignataro E, Piccioni MG, Zicari AM, Anania C. Molecular Mechanism and Clinical Effects of Probiotics in the Management of Cow's Milk Protein Allergy. Int J Mol Sci 2023; 24:9781. [PMID: 37372929 DOI: 10.3390/ijms24129781] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 05/23/2023] [Accepted: 05/31/2023] [Indexed: 06/29/2023] Open
Abstract
Cow's milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or "dysbiosis". Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics' efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms.
Collapse
Affiliation(s)
- Ludovica Cela
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Giulia Brindisi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandro Gravina
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesca Pastore
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Antonio Semeraro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Ivana Bringheli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Lavinia Marchetti
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Rebecca Morelli
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Bianca Cinicola
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Martina Capponi
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandra Gori
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Elia Pignataro
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Maria Grazia Piccioni
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Anna Maria Zicari
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| | - Caterina Anania
- Department of Maternal Infantile and Urological Science, Sapienza University of Rome, 00161 Rome, Italy
| |
Collapse
|
22
|
Wang X, Wang H, Ye Y, Yang P, Liu G, Hu Y, Tu Z. Ultrasound-assisted glycation and the allergenicity of α-lactalbumin. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:3830-3839. [PMID: 36303537 DOI: 10.1002/jsfa.12293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/30/2022] [Accepted: 10/28/2022] [Indexed: 05/03/2023]
Abstract
BACKGROUND Ultrasound-assisted glycation is a promising method for decreasing the allergenicity of α-lactalbumin (ALA). However, there is a lack of in vivo studies on the allergenicity of ultrasound-assisted glycated ALA. In this study, the effects of the ultrasound-assisted glycation of ALA on the allergenicity and intestinal microflora were characterized using a BALB/c mouse model. RESULTS Increased immunoglobulin -G/ immunoglobulin-E (IgG/IgE) and interleukin-4/6 (IL-4/6) secretions, and reduced interferon-γ (IFN-γ) secretions were found in the serum of ALA sensitized and challenged, mice in comparison with a control group. However, there was no significant difference between the mice fed with ultrasound-assisted glycated ALA and the control group. Mice that were sensitized and challenged with ALA showed disrupted intestinal microflora, manifesting in significantly decreased Firmicutes and significantly increased Proteobacteria. It was found that 100ALA-gal could maintain the intestinal microflora of mice in a normal state. Pearson's rank correlation showed that Proteobacteria and Spirochaetota were correlated positively with the IL-4/IL-6 level and were correlated negatively with the expression of IFN-γ. Proteobacteria were also significantly positively correlated with IL-6 and negatively correlated with IFN-γ (P < 0.05). CONCLUSION These results suggested that ultrasound-assisted glycation on ALA can maintain the intestinal microflora in a normal state thus balancing the proportion of Th1/Th2 to decrease allergic reaction. © 2022 Society of Chemical Industry.
Collapse
Affiliation(s)
- Xumei Wang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Hui Wang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Yunhua Ye
- National R&D Branch Center for Conventional Freshwater Fish Processing, Jiangxi Normal University, Nanchang, China
- Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, China
| | - Ping Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Guangxian Liu
- Institute of Food Science and Technology, Jiangxi Academy of Agricultural Sciences, Nanchang, China
| | - Yueming Hu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Zongcai Tu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
- National R&D Branch Center for Conventional Freshwater Fish Processing, Jiangxi Normal University, Nanchang, China
- Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, China
| |
Collapse
|
23
|
Wilsey MJ, Florio J, Beacker J, Lamos L, Baran JV, Oliveros L, Sriaroon P, Brown JM, Vanderhoof JA. Extensively Hydrolyzed Formula Improves Allergic Symptoms in the Short Term in Infants with Suspected Cow’s Milk Protein Allergy. Nutrients 2023; 15:nu15071677. [PMID: 37049517 PMCID: PMC10096968 DOI: 10.3390/nu15071677] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/24/2023] [Accepted: 03/28/2023] [Indexed: 04/01/2023] Open
Abstract
Although extensively hydrolyzed formula is widely accepted for managing cow’s milk protein allergy (CMPA) long-term, there is a lack of evidence on its short-term efficacy. This study’s objective was to investigate the short-term symptom changes (within 3–6 weeks) of infants diagnosed with CMPA and managed with extensively hydrolyzed formula containing Lactobacillus rhamnosus at their subsequent physician visit. Healthcare providers treating 202 patients diagnosed with CMPA under six months old completed de-identified surveys, which were then analyzed in this prospective study. After their first visit, the patients were started on extensively hydrolyzed formula, and their baseline symptoms were scored on a severity scale of 0–3. Patients were then reevaluated at their next follow-up visit to assess changes in symptom severity. The study found statistically significant improvements in gastrointestinal (93%), skin (83%), respiratory (73%), and uncategorized symptoms (90%). These symptom improvements were consistent across different follow-up visit durations. This study is the largest prospective analysis conducted in the United States evaluating short-term change in CMPA symptoms severity in infants under six months old using extensively hydrolyzed formula. These findings suggest that extensively hydrolyzed formula is associated with clinical symptom relief, which is often noticeable by the next follow-up visit. However, additional randomized control trials are needed to validate these results.
Collapse
|
24
|
Melnik BC, Stadler R, Weiskirchen R, Leitzmann C, Schmitz G. Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma. Int J Mol Sci 2023; 24:ijms24076102. [PMID: 37047075 PMCID: PMC10094152 DOI: 10.3390/ijms24076102] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/05/2023] [Accepted: 03/16/2023] [Indexed: 03/29/2023] Open
Abstract
Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.
Collapse
|
25
|
Koksal ZG, Uysal P, Mercan A, Bese SA, Erge D. Does maternal fermented dairy products consumption protect against cow's milk protein allergy in toddlers? Ann Allergy Asthma Immunol 2023; 130:333-339. [PMID: 36563745 DOI: 10.1016/j.anai.2022.12.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/01/2022] [Accepted: 12/09/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Cow's milk protein allergy (CMPA) is the most common immunoglobulin E-mediated food allergy in childhood. OBJECTIVE To investigate the potential impact on the disease of the frequency, amount, and diversity of maternal consumption of fermented dairy products (FDP) during pregnancy and lactation in children with immunoglobulin E-mediated CMPA. METHODS One hundred sixty toddlers (80 with physician-diagnosed CMPA and 80 healthy controls) and their mothers participated in this case-control study. The data were collected using a structured questionnaire and were compared between the 2 groups. RESULTS The most commonly consumed FDP were cheese, yogurt, and tarhana. The amounts of maternal yogurt, tarhana, and kefir consumed during pregnancy (P < .001, P < .001, and P = .04, respectively) in addition to yogurt and tarhana consumption during lactation (P < .001 and P = .001, respectively) were lower in toddlers with CMPA. The frequency of maternal consumption of yogurt, cheese, and tarhana during lactation (P = .001, P = .003, and P = .02, respectively) and the diversity of FDP were also lower in toddlers with CMPA (P = .001). At multivariate logistic regression analysis, maternal weight gain during pregnancy (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.18; P = .001), maternal age (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and gestational age at birth (OR, 1.23; 95% CI, 1.03-1.48; P = .02) increased the odds of the baby having CMPA. The diversity of FDP consumed during lactation was protective against CMPA (OR, 0.439; 95% CI, 0.272-0.711; P = .001). CONCLUSION Weekly maternal consumption of FDP was low during pregnancy and lactation in toddlers with CMPA. Although the diversity of FDP consumed during lactation may reduce the risk of CMPA, this effect was not observed during pregnancy.
Collapse
Affiliation(s)
- Zeynep Gulec Koksal
- Aydin Adnan Menderes University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Aydin, Turkey.
| | - Pinar Uysal
- Aydin Adnan Menderes University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Aydin, Turkey
| | - Adnan Mercan
- Aydin Adnan Menderes University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Aydin, Turkey
| | - Simge Atar Bese
- Aydin Adnan Menderes University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Aydin, Turkey
| | - Duygu Erge
- Aydin Adnan Menderes University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Aydin, Turkey
| |
Collapse
|
26
|
Seidita A, Mansueto P, Giuliano A, Chiavetta M, Soresi M, Carroccio A, the Internal Medicine Study Group. Fecal Calprotectin in Self-Reported Milk Intolerance: Not Only Lactose Intolerance. Nutrients 2023; 15:1048. [PMID: 36839406 PMCID: PMC9962554 DOI: 10.3390/nu15041048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/13/2023] [Accepted: 02/18/2023] [Indexed: 02/22/2023] Open
Abstract
The hypothesis is that inflammatory/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a "positive" intestinal inflammation marker and its correlation with lactose tolerance/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive/negative results (maldigester/digester) and the presence/absence of symptoms reported during LHBT (intolerant/tolerant), patients were divided into: 'lactose tolerants' (n. 104), 'maldigesters/intolerants' (n. 187), 'digesters/intolerants' (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (>15%), extraintestinal symptoms (>30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (>50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters/intolerants had higher positivity frequencies (p < 0.0001, for both) and absolute values (p = 0.04, for maldigesters/intolerants) of FCP compared to digesters/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients.
Collapse
Affiliation(s)
- Aurelio Seidita
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90120 Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Pasquale Mansueto
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Alessandra Giuliano
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90120 Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Marta Chiavetta
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90120 Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Maurizio Soresi
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90120 Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | | |
Collapse
|
27
|
Bedolla-Pulido A, Morales-Romero J, Hernández-Colín DD, Bedolla-Pulido TR, Meza-López C, Bedolla-Barajas M. [Prevalence of cow´s milk allergy and lactose intolerance among Mexican late adolescents]. REVISTA ALERGIA MÉXICO 2023; 69:105-108. [PMID: 36869009 DOI: 10.29262/ram.v69i3.1120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 09/28/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE To determine the prevalence of cow´s milk allergy and lactose intolerance in a sample of late adolescents. METHODS Through a population-based study, data corresponding to students with aged 15 to 18 years were analyzed. RESULTS A total of 1992 adolescents was analized. The prevalence of cow´s milk allergy was 1.4% (95% CI: 0.2% to 0.8%) and the prevalence of lactose intolerance was 0.5% (95% CI: 0.2% to 0.8%). Adolescents with cow´s milk allergy had fewer gastrointestinal symptoms (p = 0.036), but more skin (p < 0.001) and respiratory (p = 0.028) ailments than adolescents with lactose intolerance. CONCLUSIONS The manifestations associated with cow's milk consumption in late adolescents seem to correspond mainly to cow´s milk allergy than to lactose intolerance.
Collapse
Affiliation(s)
- Angie Bedolla-Pulido
- Universidad de Guadalajara, Centro Universitario en Ciencias de la Salud, Guadalajara, Jalisco.
| | | | - Dante Daniel Hernández-Colín
- División de Medicina Interna, Servicio de Alergia e Inmunología Clínica. Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Jalisco.
| | | | - Carlos Meza-López
- Servicio de Pediatría. Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Jalisco.
| | - Martín Bedolla-Barajas
- División de Medicina Interna, Servicio de Alergia e Inmunología Clínica. Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Jalisco.
| |
Collapse
|
28
|
Gurung M, Rosa F, Yelvington B, Terry N, Read QD, Piccolo BD, Moody B, Tripp P, Pittman HE, Fay BL, Ross TJ, Sikes JD, Flowers JB, Fox R, LeRoith T, Talatala R, Bar-Yoseph F, Yeruva L. Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model. Nutrients 2023; 15:383. [PMID: 36678256 PMCID: PMC9861483 DOI: 10.3390/nu15020383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/10/2023] [Accepted: 01/11/2023] [Indexed: 01/14/2023] Open
Abstract
A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.
Collapse
Affiliation(s)
- Manoj Gurung
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Fernanda Rosa
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
- School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79409, USA
| | - Brooke Yelvington
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Nathan Terry
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Quentin D. Read
- USDA-ARS, Southeast Area, North Carolina State University, Raleigh, NC 27695, USA
| | - Brian D. Piccolo
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Becky Moody
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Patricia Tripp
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Hoy E. Pittman
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Bobby L. Fay
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Talyor J. Ross
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - James D. Sikes
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | | | - Renee Fox
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | - Tanya LeRoith
- Department of Biomedical Sciences & Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA
| | - Rachelanne Talatala
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| | | | - Laxmi Yeruva
- USDA-ARS, South East Area, Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA
| |
Collapse
|
29
|
Ribes-Koninckx C, Amil-Dias J, Espin B, Molina M, Segarra O, Diaz-Martin JJ. The use of amino acid formulas in pediatric patients with allergy to cow's milk proteins: Recommendations from a group of experts. Front Pediatr 2023; 11:1110380. [PMID: 37033186 PMCID: PMC10073469 DOI: 10.3389/fped.2023.1110380] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/01/2023] [Indexed: 04/11/2023] Open
Abstract
One of the most common food allergies in children is cow's milk allergy (CMA). In breast-fed infants with CMA, the mother is encouraged to avoid dairy products. If this is not possible, or in formula fed infants, use of hypoallergenic replacement formulas such as extensively hydrolyzed formulas (EHF) is recommended. However, in ∼5% of patients EHFs are not tolerated and/or allergy symptoms can persist. When EHFs are ineffective and in severe forms of CMA, amino acid-based formulas (AAF) should be considered. Six pediatric gastroenterologists with extensive experience in food allergy management reviewed scientific publications and international clinical practice guidelines to provide practical recommendations on AAF. The guidelines reviewed had discrepancies and ambiguities around the specific indications for using formulas as a milk substitute. The panel recommends AAFs as the first therapeutic option in anaphylaxis due to CMA, in acute and chronic severe food protein-induced enterocolitis syndrome, in CMA associated with multiple food allergy, and in cases of eosinophilic esophagitis not responding to an extended exclusion diet or not eating solids. The main benefit of AAF is its absence of residual allergenicity, making it a safe treatment option in severe CMA patients who do not tolerate or respond to an EHF.
Collapse
Affiliation(s)
- Carmen Ribes-Koninckx
- Pediatric Gastroenterology, Hepatology and Nutrition La Fe University and Politechnic Hospital & La Fe Research Institute, Valencia, Spain
- Correspondence: Carmen Ribes-Koninckx
| | - Jorge Amil-Dias
- Emeritus, S. João University Hospital Center, Porto, Portugal
| | - Beatriz Espin
- Pediatric Gastroenterology and Nutrition Unit, Virgen del Rocio University Hospital, Seville, Spain
| | - Manuel Molina
- Department of Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain
| | - Oscar Segarra
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Juan J. Diaz-Martin
- Pediatric Gastroenterology and Nutrition, Hospital Universitario Central de Asturias, Oviedo, Spain
| |
Collapse
|
30
|
Lactose-Containing Dry-Powder Inhalers for Patients with Cow's Milk Protein Allergy-The Conundrum; A National Survey of Pediatric Pulmonologists and Allergologists. J Clin Med 2022; 11:jcm11247346. [PMID: 36555964 PMCID: PMC9785354 DOI: 10.3390/jcm11247346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/28/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Introduction: Several dry-powder inhalers (DPIs) contain lactose which may be contaminated with milk proteins. Confusion exists pertaining to DPI use in patients with cow's milk protein allergy (CMPA). Methods: A computerized survey sent via e-mail to pediatric pulmonologists and allergologists. Results: A total of 77 out of 232 (33.2%) doctors replied, of whom 80.5% were pediatric pulmonologists. A total of 69 of 77 (89.6%) were specialists, 37.6% with more than 15 years of experience. The most commonly used DPIs were formoterol + budesonide and vilanterol + fluticasone. A total of 62 out of 77 (80.5%) responders knew these DPIs contained lactose. A total of 35 out of 77 (45.5%) doctors who replied did not know that DPI leaflets list CMPA as a contra-indication to DPI administration. Of these, 4 (11.4%) stated that they would instruct patients with CMPA to stop DPIs, and 7 (20%) would avoid recommending DPIs. A total of 42 out of 77 (54.5%) responders were aware of this warning, yet 13 of these 42 (30.9%) continued to recommend lactose-containing DPIs without hesitation and 18 of these 42 (42.8%) responders prescribed DPIs but considered allergy severity. Conclusions: Almost half of certified, experienced pediatric pulmonologists and allergologists were unaware of the warning to administer DPIs to patients with CMPA. Most doctors who do know of this warning still continue to prescribe these DPIs.
Collapse
|
31
|
Cresoe S, Setya A, Beasley G, Gonzalo DH, Chan A. Unusual Presentation of Cow's Milk Protein Allergy. JPGN REPORTS 2022; 3:e246. [PMID: 37168480 PMCID: PMC10158318 DOI: 10.1097/pg9.0000000000000246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 07/11/2022] [Indexed: 05/13/2023]
Abstract
Cow's milk protein allergy (CMPA) is an abnormal immunologic response to bovine protein that can result in various gastrointestinal and cutaneous manifestations including diarrhea, failure to thrive, malabsorption, and even protein-losing enteropathy. We describe a case of a 7-month-old breastfed male who presented with severe atopic dermatitis, emesis, oily diarrhea, failure to thrive, electrolyte disturbance, and hemodynamic instability. Following stabilization, additional evaluation revealed concern for abetalipoproteinemia. Ultimately, the patient's symptoms resolved with introduction of an elemental formula and returned with reinitiation of cow's milk protein, confirming the diagnosis of severe CMPA. It is important for the general practitioner to be aware of the various presentations and have a high index of suspicion for CMPA as no symptom or diagnostic test is pathognomonic for diagnosis. Even though it can mimic other causes of malabsorption, a trial with extensively hydrolyzed or elemental formula should be attempted before undertaking invasive testing.
Collapse
Affiliation(s)
- Samantha Cresoe
- From the Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL
| | - Aniruddh Setya
- Department of Pediatric Gastroenterology, Kidz Medical Services, Miami, FL
| | - Genie Beasley
- From the Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL
| | | | - Albert Chan
- From the Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL
| |
Collapse
|
32
|
Yang F, Ma X, Hu W, Xiong Z, Huang M, Wu Y, Meng X, Wu Z, Yang A, Li X, Chen H. Identification of immunoglobulin E epitopes on major allergens from dairy products after digestion and transportation in vitro. J Dairy Sci 2022; 105:9476-9487. [DOI: 10.3168/jds.2022-22287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 07/29/2022] [Indexed: 11/05/2022]
|
33
|
Weimer DS, Demory Beckler M. Underlying Immune Mechanisms Involved in Cow’s Milk-Induced Hypersensitivity Reactions Manifesting as Atopic Dermatitis. Cureus 2022; 14:e27604. [PMID: 36059314 PMCID: PMC9433788 DOI: 10.7759/cureus.27604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/02/2022] [Indexed: 11/26/2022] Open
Abstract
Of the many symptoms associated with cow’s milk allergy (CMA), many populations face the burden of the appearance or worsening of atopic dermatitis (AD) when consuming milk products. Due to the prevalence and possible severity of symptoms, it is important to understand the underlying immune mechanisms involved in such reactions. Hypersensitivity reactions are exaggerated immune responses to often benign antigens, many times resulting in a cascade of pro-inflammatory processes. Of the four major types, type I and IV are of most relevance when considering atopic dermatitis worsened by cow’s milk. Considered a “true allergy,” type I (immediate) hypersensitivity reactions occur within hours after secondary exposure to an allergen and are primarily driven by antibodies and humoral immune responses. On the contrary, type IV (delayed) hypersensitivity reactions are driven by cell-mediated responses involving T-cell activation. Due to the array of symptoms induced by these complex reactions, it is imperative to diagnose early and treat appropriately. In this literature review, we aim to highlight the primary underlying immune contributors to hypersensitivity reactions, discuss AD as a manifestation of hypersensitivity reactions to cow’s milk, and consider current and future treatment options for combatting hypersensitivities manifesting as AD.
Collapse
|
34
|
Zamanillo-Campos R, Coto Alonso L, Fuentes Martín MJ, Nevot Escusa P, Tejón Fernández M. Nutritional counseling for cow's milk protein allergy in infants from birth to 2 y of ages: Scoping review. Nutrition 2022; 98:111633. [PMID: 35447465 DOI: 10.1016/j.nut.2022.111633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/29/2022] [Accepted: 02/09/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Cow's milk protein allergy (CMPA) is a clinical condition that requires appropriate nutritional counseling during breastfeeding and the introduction of complementary feeding. Using evidence-based dietetic advice is critical for correct growth and development during childhood. The aim of this study was to review the most recent literature on nutritional counseling aimed at infants between 0 and 2 y of age diagnosed with CMPA. METHODS Six databases were searched and updated on August 22, 2020. Retrieved articles were screened in duplicate and independently by all the authors, and these were selected according to the following inclusion criteria: clinical trials, reviews, meta-analyses, and clinical practice guidelines published since 2013 on any dietetic intervention aimed at infant populations between 0 and 2 y of age with CMPA. Critical appraisal through the AGREE instrument and CASP tools enabled the risk of bias assessment. RESULTS We obtained 2874 results, of which 40 were included for reviewing. The retrieved information enabled us to answer all the research questions, including aspects of the nutritional counseling aimed at mothers who breastfeed infants with CMPA, as well as infants during breastfeeding and the introduction of complementary feeding. We also reviewed the specific nutritional requirements of infants with CMPA to assess nutritional supplementation and the evidence available on the use of probiotics, prebiotics, and symbiotics. CONCLUSIONS This scoping review collected, in a structured and comprehensive way, the most recent available information regarding nutritional counseling in CMPA for a successful dietetic intervention of the casuistry that may arise during early infancy.
Collapse
Affiliation(s)
- Rocío Zamanillo-Campos
- Specialization Group in Pediatric Nutrition of the Spanish Academy of Nutrition and Dietetics (AEND), Navarra, Spain; Health Research Institute of the Balearic Islands (IdISBa), Balearic Islands, Spain.
| | - Laura Coto Alonso
- Specialization Group in Pediatric Nutrition of the Spanish Academy of Nutrition and Dietetics (AEND), Navarra, Spain; Biomedal SL., Sevilla, Spain; Human Nutrition and Food Science Department, University of Granada, Granada, Spain.
| | - María Jesús Fuentes Martín
- Specialization Group in Pediatric Nutrition of the Spanish Academy of Nutrition and Dietetics (AEND), Navarra, Spain; Plexos Clinic, Teruel, Spain.
| | - Patricia Nevot Escusa
- Specialization Group in Pediatric Nutrition of the Spanish Academy of Nutrition and Dietetics (AEND), Navarra, Spain; Nutrition Center Júlia Farré, Barcelona, Spain.
| | - Marta Tejón Fernández
- Specialization Group in Pediatric Nutrition of the Spanish Academy of Nutrition and Dietetics (AEND), Navarra, Spain; Paediatric Gastroenterology and Nutrition Unit, Children's & Women's Hospital, Almería, Spain.
| |
Collapse
|
35
|
Wang XM, Tu ZC, Ye YH, Liu GX, Hu YM, Wang H. Isolation and allergenicity evaluation of glycated α-lactalbumin digestive products and identification of allergenic peptides. Food Chem 2022; 390:133185. [PMID: 35567971 DOI: 10.1016/j.foodchem.2022.133185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 04/27/2022] [Accepted: 05/06/2022] [Indexed: 02/01/2023]
Abstract
This study aimed to isolate and evaluate the allergenicity of glycated α-lactalbumin (ALA) digestive products and identify its allergenic peptides. The digestive products of native-, alone glycated- and ultrasound-assisted glycated ALA (ALA-D, ALA-gal-D, 100ALA-gal-D) were isolated into three fractions (F1, F2 and F3). High-resolution mass spectrometry showed that the digestion-resistant peptides of F2 and F3 mainly distributed in amino acid sequence (AA) 25-31, AA32-53, AA40-53, AA54-60, AA80-90, AA94-104. The allergenicity of the three fractions of glycated ALA was lower than that in ALA-D, indicating glycation of ALA could indeed reduce its allergenicity after digestion. Furthermore, most fractions isolated from high glycation-degree ALA had the lowest allergenicity. The IgG/IgE binding abilities of synthesized peptides indicated that AA94-104 firstly identified by us embodied the strongest allergenicity and might be the potential allergenic peptide. This will provide a theory for preparing hypoallergenic products based on the identified allergenic peptides.
Collapse
Affiliation(s)
- Xu-Mei Wang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Zong-Cai Tu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China; National R&D Branch Center for Conventional Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
| | - Yun-Hua Ye
- National R&D Branch Center for Conventional Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Engineering Research Center of Freshwater Fish High-value Utilization of Jiangxi Province, Jiangxi Normal University, Nanchang, Jiangxi 330022, China
| | - Guang-Xian Liu
- Institute of Food Science and Technology, Jiangxi Academy of Agricultural Sciences, Nanchang 330200, China
| | - Yue-Ming Hu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Hui Wang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
| |
Collapse
|
36
|
Toca MC, Morais MB, Vázquez-Frias R, Becker-Cuevas DJ, Boggio-Marzet CG, Delgado-Carbajal L, Higuera-Carrillo MM, Ladino L, Marchisone S, Messere GC, Ortiz GJ, Ortiz-Paranza LR, Ortiz-Piedrahita C, Riveros-López JP, Sosa PC, Villalobos-Palencia NC. Consensus on the diagnosis and treatment of cow's milk protein allergy of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:235-250. [PMID: 35623990 DOI: 10.1016/j.rgmxen.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/05/2022] [Indexed: 11/15/2022]
Abstract
Cow's milk protein allergy (CMPA) is the most frequent cause of food allergy in the first months of life. Despite the fact that there are different guidelines and recommendations on the management of children with CMPA, there continues to be great variability in diagnostic and therapeutic criteria in Latin America. The Food Allergy Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition summoned a group of Latin American experts to reach a consensus and formulate a document to unify diagnostic and therapeutic criteria for CMPA. Three teams were formed, each with a coordinator, and the members of each team developed a series of statements for their corresponding module: a) clinical manifestations and diagnosis; b) diagnostic tools, and c) treatment. A search of the medical literature was carried out to support the information presented in each module and 28 statements were then selected. The statements were discussed, after which they were evaluated by all the experts, utilizing the Delphi method. Their opinions on statement agreement or disagreement were anonymously issued. The final statements selected were those with above 75% agreement and their corresponding recommendations were formulated, resulting in the document presented herein.
Collapse
Affiliation(s)
- M C Toca
- Sección Gastroenterología, Hepatología y Nutrición, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina
| | - M B Morais
- Escuela Paulista de Medicina, Universidad Federal de Sao Paulo, Sao Paulo, Brazil
| | - R Vázquez-Frias
- Departamento de Gastroenterología y Nutrición, Instituto Nacional de Salud Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
| | - D J Becker-Cuevas
- Servicio de Pediatría, Hospital de Clínicas, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | - C G Boggio-Marzet
- Gastroenterología y Nutrición Pediátrica, División Pediatría, Departamento Materno Infanto Juvenil, Hospital Gral. de Agudos «Dr. I. Pirovano», Ciudad Autónoma de Buenos Aires, Argentina
| | - L Delgado-Carbajal
- Servicio de Gastroenterología, Hepatología y Nutrición Pediátrica, Unidad de Endoscopia Digestiva Pediátrica, Hospital Universitario «Centro Hospitalario Pereira Rossell», Montevideo, Uruguay
| | | | - L Ladino
- Instituto de Investigación en Nutrición, Genética y Metabolismo IINGM, Facultad de Medicina, Universidad El Bosque, Bogotá, Colombia
| | - S Marchisone
- Servicio de Gastroenterología, Hospital Infantil de Córdoba, Córboba, Argentina
| | - G C Messere
- Sección Gastroenterología, Hepatología y Nutrición, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina
| | - G J Ortiz
- Sección de Gastroenterología, Hepatología y Nutrición Infantil, Servicio de Pediatría, Hospital Nacional Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - L R Ortiz-Paranza
- Hospital General Pediátrico «Niños de Acosta Ñu», Ministerio de Salud Pública y Bienestar Social, San Lorenzo, Paraguay
| | - C Ortiz-Piedrahita
- Departamento de Pediatría, Servicio de Gastroenterología Infantil, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - J P Riveros-López
- Unidad de Gastroenterología Pediátrica Juan Pablo Riveros SAS, Bogotá, Colombia
| | - P C Sosa
- Sección Gastroenterología, Hepatología y Nutrición Infantil, Servicio de Pediatría, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina
| | | |
Collapse
|
37
|
García Sánchez P, Santos Simarro G, Sampredro Martín M, Valladares Salado L, Escolano Taravillo L. A Cyanotic Infant: Infrequent Presentation of Cow’s Milk Protein Allergy. Cureus 2022; 14:e21678. [PMID: 35242464 PMCID: PMC8884543 DOI: 10.7759/cureus.21678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2022] [Indexed: 11/16/2022] Open
Abstract
We report the case of a three-month-old boy who presented with poor weight gain, loose stools, and poor oral intake for three weeks. Physical examination revealed a pale infant with abdominal distension and cyanosis. Oxygen saturation was normal, but the laboratory showed important methemoglobinemia. The diagnosis of FPIES (food protein-induced enterocolitis syndrome) in the context of cow’s milk protein allergy (CMPA) was suspected. Although CMPA is a common condition encountered in small children, chronic forms of FPIES can be difficult to diagnose. Maintaining clinical suspicion about the potential association between methemoglobinemia and gastrointestinal symptoms can lead to prompt recognition and intervention.
Collapse
|
38
|
Dodi G, Di Filippo P, Di Pillo S, Chiarelli F, Attanasi M. Total serum IgE levels as predictor of the acquisition of tolerance in children with food allergy: Findings from a pilot study. Front Pediatr 2022; 10:1013807. [PMID: 36340719 PMCID: PMC9630731 DOI: 10.3389/fped.2022.1013807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The gold standard to diagnose food allergy (FA) is a double-blind, placebo-controlled food challenge (OFC), even if it shows potential risk of severe allergic reactions for the patient and is time-consuming. Therefore, easier, and less invasive methods are needed to diagnose FA and predict the tolerance, changing the clinical practice. AIM The main aim of this study was to assess whether the total IgE values at the diagnosis of FA were associated with the duration of the tolerance acquisition and thus of the food elimination diet. METHODS We retrospectively analyzed the medical records of 40 patients allergic to milk or egg who performed an OFC for the reintroduction of the causal food at the Pediatric Allergy and Respiratory Unit of the University of Chieti from January 2018 to December 2020. RESULTS We found a positive association of total serum IgE with the elimination diet duration (β = 0.152; CI, 95% 0.04-0.27) after adjusting for age, sex, and type of allergy (milk or egg). We also showed a significant correlation (r = 0.41 and p-value = 0.007) between the total IgE values and the duration of the elimination diet and a significant correlation between the casein specific IgE values at diagnosis of FA and the severity of the clinical presentation (r = 0.66; p-value 0.009). CONCLUSION Total serum IgE at baseline, along with the downward trend of food-specific IgE levels (to milk or egg), may be useful in the prognostication of natural tolerance acquisition.
Collapse
Affiliation(s)
- Giulia Dodi
- Department of Pediatrics, Pediatric Allergy and Pulmonology Unit, University of Chieti-Pescara, Chieti, Italy
| | - Paola Di Filippo
- Department of Pediatrics, Pediatric Allergy and Pulmonology Unit, University of Chieti-Pescara, Chieti, Italy
| | - Sabrina Di Pillo
- Department of Pediatrics, Pediatric Allergy and Pulmonology Unit, University of Chieti-Pescara, Chieti, Italy
| | - Francesco Chiarelli
- Department of Pediatrics, Pediatric Allergy and Pulmonology Unit, University of Chieti-Pescara, Chieti, Italy
| | - Marina Attanasi
- Department of Pediatrics, Pediatric Allergy and Pulmonology Unit, University of Chieti-Pescara, Chieti, Italy
| |
Collapse
|
39
|
Zurzolo GA, Campbell DE, Said M, Peters RL, Dharmage SC. Anaphylaxis to foods purchased from food establishments in Australia. J Paediatr Child Health 2022; 58:77-82. [PMID: 34260784 DOI: 10.1111/jpc.15651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/23/2021] [Accepted: 07/06/2021] [Indexed: 11/29/2022]
Abstract
AIM Food establishments that sell non-packaged foods are not required to have a food label directly on the food product detailing the ingredients. This practice could increase the risk of anaphylaxis among individuals with food allergy. The aim of the study is to understand whether anaphylaxis occurs commonly in individuals with food allergy as a consequence of eating food products purchased from food establishments. METHODS We undertook an anonymous on-line cross-sectional survey of food allergic individuals over a 9-month period. Anaphylaxis was defined as reported symptoms consistent with the Australasian Society of Clinical Immunology and Allergy definition of anaphylaxis. RESULTS A total of 268 responses were received over the study period and 264 consented and completed the questionnaire. Among our survey participants, the rate of anaphylaxis to food purchased from establishments was 27% (n = 67/246, 95% confidence interval 21.8-33.3%). Of those who reported an anaphylaxis (n = 67), 87% reported informing staff of their/their dependents food allergy/s. Most (81%) reported that they would like to see additional information, such as listing of allergen information next to dishes on the menu and 61% reported that staff pro-actively asking about food allergies would be beneficial. CONCLUSION Anaphylaxis from food purchased at food establishments is not uncommon despite a high proportion of individuals declaring their food allergy to staff. Consumers with food allergy would like to see allergen information listed on the menus and for staff to proactively enquire about food allergies. A food allergen matrix that is regularly checked/updated so staff and consumers have easy access to information on menu items and common allergens is required.
Collapse
Affiliation(s)
- Giovanni A Zurzolo
- Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.,Centre for Food & Allergy Research (CFAR), Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Dianne E Campbell
- Centre for Food & Allergy Research (CFAR), Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Allergy and Immunology The Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia
| | - Maria Said
- Allergy & Anaphylaxis Australia, Sydney, New South Wales, Australia
| | - Rachel L Peters
- Centre for Food & Allergy Research (CFAR), Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Shyamali C Dharmage
- Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
40
|
Zhang Y, Li L, Genest G, Zhao W, Ke D, Bartolucci S, Pavey N, Al-Aubodah TA, Lejtenyi D, Torabi B, Ben-Shoshan M, Mazer B, Piccirillo CA. Successful Milk Oral Immunotherapy Promotes Generation of Casein-Specific CD137 + FOXP3 + Regulatory T Cells Detectable in Peripheral Blood. Front Immunol 2021; 12:705615. [PMID: 34887847 PMCID: PMC8650635 DOI: 10.3389/fimmu.2021.705615] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 10/04/2021] [Indexed: 11/13/2022] Open
Abstract
Background Oral immunotherapy (OIT) is an emerging treatment for cow's milk protein (CMP) allergy in children. The mechanisms driving tolerance following OIT are not well understood. Regulatory T cells (TREG) cells are key inhibitors of allergic responses and promoters of allergen-specific tolerance. In an exploratory study, we sought to detect induction of allergen-specific TREG in a cohort of subjects undergoing OIT. Methods Pediatric patients with a history of allergic reaction to cow's milk and a positive Skin Pick Test (SPT) and/or CMP-specific IgE >0.35 kU, as well as a positive oral challenge to CMP underwent OIT with escalating doses of milk and were followed for up to 6 months. At specific milestones during the dose escalation and maintenance phases, casein-specific CD4+ T cells were expanded from patient blood by culturing unfractionated PBMCs with casein in vitro. The CD4+ T cell phenotypes were quantified by flow cytometry. Results Our culture system induced activated casein-specific FOXP3+Helios+ TREG cells and FOXP3- TEFF cells, discriminated by expression of CD137 (4-1BB) and CD154 (CD40L) respectively. The frequency of casein-specific TREG cells increased significantly with escalating doses of milk during OIT while casein-specific TEFF cell frequencies remained constant. Moreover, expanded casein-specific TREG cells expressed higher levels of FOXP3 compared to polyclonal TREG cells, suggesting a more robust TREG phenotype. The induction of casein-specific TREG cells increased with successful CMP desensitization and correlated with increased frequencies of casein-specific Th1 cells among OIT subjects. The level of casein-specific TREG cells negatively correlated with the time required to reach the maintenance phase of desensitization. Conclusions Overall, effective CMP-OIT successfully promoted the expansion of casein-specific, functionally-stable FOXP3+ TREG cells while mitigating Th2 responses in children receiving OIT. Our exploratory study proposes that an in vitro TREG response to casein may correlate with the time to reach maintenance in CMP-OIT.
Collapse
Affiliation(s)
- Yi Zhang
- Department of Otolaryngology-Head and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lei Li
- Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | | | - Wei Zhao
- Program in Translational Research in Respiratory Diseases, Research Institute of the McGill University Health Centre, Montréal, QC, Canada
| | - Dan Ke
- Program in Translational Research in Respiratory Diseases, Research Institute of the McGill University Health Centre, Montréal, QC, Canada
| | - Sabrina Bartolucci
- Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.,Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada
| | - Nils Pavey
- Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.,Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada
| | - Tho-Alfakar Al-Aubodah
- Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.,Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada
| | - Duncan Lejtenyi
- Division of Allergy Immunology and Clinical Dermatology, Montreal Children's Hospital, McGill University, Montréal, QC, Canada
| | - Bahar Torabi
- Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Division of Allergy Immunology and Clinical Dermatology, Montreal Children's Hospital, McGill University, Montréal, QC, Canada
| | - Moshe Ben-Shoshan
- Division of Allergy Immunology and Clinical Dermatology, Montreal Children's Hospital, McGill University, Montréal, QC, Canada
| | - Bruce Mazer
- Program in Translational Research in Respiratory Diseases, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada.,Division of Allergy Immunology and Clinical Dermatology, Montreal Children's Hospital, McGill University, Montréal, QC, Canada
| | - Ciriaco A Piccirillo
- Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.,Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.,Centre of Excellence in Translational Immunology (CETI), Montréal, QC, Canada
| |
Collapse
|
41
|
El-Hodhod MA, El-Shabrawi MHF, AlBadi A, Hussein A, Almehaidib A, Nasrallah B, AlBassam EM, El Feghali H, Isa HM, Al Saraf K, Sokhn M, Adeli M, Al-Sawi NMM, Hage P, Al-Hammadi S. Consensus statement on the epidemiology, diagnosis, prevention, and management of cow's milk protein allergy in the Middle East: a modified Delphi-based study. World J Pediatr 2021; 17:576-589. [PMID: 34817828 PMCID: PMC8639571 DOI: 10.1007/s12519-021-00476-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/17/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND This study aimed to develop an expert consensus regarding the epidemiology, diagnosis, and management of cow's milk protein allergy (CMPA) in the Middle East. METHODS A three-step modified Delphi method was utilized to develop the consensus. Fifteen specialized pediatricians participated in the development of this consensus. Each statement was considered a consensus if it achieved an agreement level of ≥ 80%. RESULTS The experts agreed that the double-blind placebo-controlled oral challenge test (OCT) should be performed for 2-4 weeks using an amino acid formula (AAF) in formula-fed infants or children with suspected CMPA. Formula-fed infants with confirmed CMPA should be offered a therapeutic formula. The panel stated that an extensively hydrolyzed formula (eHF) is indicated in the absence of red flag signs. At the same time, the AAF is offered for infants with red flag signs, such as severe anaphylactic reactions. The panel agreed that infants on an eHF with resolved symptoms within 2-4 weeks should continue the eHF with particular attention to the growth and nutritional status. On the other hand, an AAF should be considered for infants with persistent symptoms; the AAF should be continued if the symptoms resolve within 2-4 weeks, with particular attention to the growth and nutritional status. In cases with no symptomatic improvements after the introduction of an AAF, other measures should be followed. The panel developed a management algorithm, which achieved an agreement level of 90.9%. CONCLUSION This consensus document combined the best available evidence and clinical experience to optimize the management of CMPA in the Middle East.
Collapse
Affiliation(s)
- Moustafa A El-Hodhod
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Faculty of Medicine, October 6 University, Giza, Egypt
| | - Mortada H F El-Shabrawi
- Faculty of Medicine, Cairo University, Cairo, Egypt
- International Pediatric Association (IPA), Marengo, USA
- International Society of Tropical Pediatrics (ISTP), Manila, Philippines
| | | | | | - Ali Almehaidib
- Pediatric Gastroenterology, Department of Pediatrics, King Faisal Specialist Hospital and Research Center Riyadh, Riyadh, Saudi Arabia
| | | | - Ebtsam Mohammed AlBassam
- Nutrition Service Department, King Faisal Specialist and Research Center Riyadh, Riyadh, Saudi Arabia
| | | | - Hasan M Isa
- Pediatric Department, Salmaniya Medical Complex, Manama, Bahrain
- Pediatric department, Arabian Gulf University, Manama, Bahrain
| | - Khaled Al Saraf
- Pediatrics Department, Dar Al Shifa Hospital, Kuwait, Kuwait
| | - Maroun Sokhn
- Pediatric Gastroenterology, Hepatology, and Nutrition Department, Saint George University Medical Center, University of Balamand, Beirut, Lebanon
| | | | | | - Pierre Hage
- Pediatric Pulmonology and Allergology, University of Balamand, Beirut, Lebanon
| | - Suleiman Al-Hammadi
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Building 14, 505055, Dubai, United Arab Emirates.
| |
Collapse
|
42
|
Sur LM, Armat I, Duca E, Sur G, Lupan I, Sur D, Samasca G, Lazea C, Lazar C. Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects. Life (Basel) 2021; 11:life11111204. [PMID: 34833080 PMCID: PMC8620930 DOI: 10.3390/life11111204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 10/26/2021] [Accepted: 11/05/2021] [Indexed: 01/01/2023] Open
Abstract
Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.
Collapse
Affiliation(s)
- Lucia M. Sur
- Department of Pediatric I, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| | - Ionel Armat
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| | - Emanuela Duca
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| | - Genel Sur
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| | - Iulia Lupan
- Molecular Biology Department, Babes Bolyai University, 400084 Cluj-Napoca, Romania;
| | - Daniel Sur
- The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania;
| | - Gabriel Samasca
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
- Department of Allergology and Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
- Correspondence:
| | - Cecilia Lazea
- Department of Pediatric I, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| | - Calin Lazar
- Department of Pediatric I, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (L.M.S.); (C.L.); (C.L.)
- Children Emergency Clinical Hospital, 400370 Cluj-Napoca, Romania; (I.A.); (E.D.); (G.S.)
| |
Collapse
|
43
|
Ahmed I, Chen H, Li J, Wang B, Li Z, Huang G. Enzymatic crosslinking and food allergenicity: A comprehensive review. Compr Rev Food Sci Food Saf 2021; 20:5856-5879. [PMID: 34653307 DOI: 10.1111/1541-4337.12855] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/24/2021] [Accepted: 09/10/2021] [Indexed: 12/19/2022]
Abstract
Food allergy has become a major global public health concern. In the past decades, enzymatic crosslinking technique has been employed to mitigate the immunoreactivity of food allergens. It is an emerging non-thermal technique that can serve as a great alternative to conventional food processing approaches in developing hypoallergenic food products, owing to their benefits of high specificity and selectivity. Enzymatic crosslinking via tyrosinase (TYR), laccase (LAC), peroxidase (PO), and transglutaminase (TG) modifies the structural and biochemical properties of food allergens that subsequently cause denaturation and masking of the antigenic epitopes. LAC, TYR, and PO catalyze the oxidation of tyrosine side chains to initiate protein crosslinking, while TG initiates isopeptide bonding between lysine and glutamine residues. Enzymatic treatment produces a high molecular weight crosslinked polymer with reduced immunoreactivity and IgE-binding potential. Crosslinked allergens further inhibit mast cell degranulation due to the lower immunostimulatory potential that assists in the equilibration of T-helper (Th)1/Th2 immunobalance. This review provides an updated overview of the studies carried out in the last decade on the potential application of enzymatic crosslinking for mitigating food allergenicity that can be of importance in the context of developing hypoallergenic/non-allergenic food products.
Collapse
Affiliation(s)
- Ishfaq Ahmed
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, P. R. China
| | - Huan Chen
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, P. R. China
| | - Jiale Li
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, P. R. China
| | - Bin Wang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, P. R. China
| | - Zhenxing Li
- College of Food Science and Engineering, Ocean University of China, Qingdao, P. R. China
| | - Gonghua Huang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, P. R. China
| |
Collapse
|
44
|
Zhao X, Thijssen S, Chen H, Garssen J, Knippels LMJ, Hogenkamp A. Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow's Milk Allergy. Nutrients 2021; 13:2479. [PMID: 34444651 PMCID: PMC8400770 DOI: 10.3390/nu13082479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 12/27/2022] Open
Abstract
Cow's milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.
Collapse
Affiliation(s)
- Xiaoli Zhao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (X.Z.); (H.C.)
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (S.T.); (J.G.); (L.M.J.K.)
- School of Food Science Technology, Nanchang University, Nanchang 330047, China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, China
| | - Suzan Thijssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (S.T.); (J.G.); (L.M.J.K.)
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (X.Z.); (H.C.)
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, China
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (S.T.); (J.G.); (L.M.J.K.)
- Danone/Nutricia Research, Global Centre of Excellence Immunology, 3584 CT Utrecht, The Netherlands
| | - Leon M. J. Knippels
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (S.T.); (J.G.); (L.M.J.K.)
- Danone/Nutricia Research, Global Centre of Excellence Immunology, 3584 CT Utrecht, The Netherlands
| | - Astrid Hogenkamp
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; (S.T.); (J.G.); (L.M.J.K.)
| |
Collapse
|
45
|
Smith NA, Germundson DL, Gao P, Hur J, Floden AM, Nagamoto-Combs K. Anxiety-like behavior and intestinal microbiota changes as strain-and sex-dependent sequelae of mild food allergy in mouse models of cow's milk allergy. Brain Behav Immun 2021; 95:122-141. [PMID: 33705867 PMCID: PMC8525516 DOI: 10.1016/j.bbi.2021.03.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/20/2021] [Accepted: 03/02/2021] [Indexed: 12/12/2022] Open
Abstract
A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders.
Collapse
Affiliation(s)
- Nicholas A Smith
- Department of Pathology, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Danielle L Germundson
- Department of Pathology, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Pan Gao
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Junguk Hur
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Angela M Floden
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| | - Kumi Nagamoto-Combs
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
| |
Collapse
|
46
|
Cow's Milk Protein Allergy as a Model of Food Allergies. Nutrients 2021; 13:nu13051525. [PMID: 33946553 PMCID: PMC8147250 DOI: 10.3390/nu13051525] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/18/2021] [Accepted: 04/26/2021] [Indexed: 01/14/2023] Open
Abstract
Cow's milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.
Collapse
|
47
|
Duan C, Ma L, Cai L, Li X, Ma F, Chen J, Huo G, Li D. Comparison of allergenicity among cow, goat, and horse milks using a murine model of atopy. Food Funct 2021; 12:5417-5428. [PMID: 33988206 DOI: 10.1039/d1fo00492a] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Due to the prevalence and severity of cow milk (CM) allergy (CMA), an ideal substitute is urgently needed to develop hypoallergenic infant formula for infants who experience anaphylaxis to typical whey-based CM formula. Goat milk (GM) and horse milk (HM) are considered appropriate substitutes; however, whether GM and HM are less allergenic than CM is unclear. In the present study, the difference in allergenicity among CM, GM, and HM was investigated using the Balb/c mouse model. The number of mice with severe respiratory symptoms was significantly lower in the GM- and HM-sensitised groups than in the CM-sensitised group. Furthermore, histologic examination of intestinal and lung tissues revealed a thinner lamina propria of the small intestine and obvious inflammation and congestion in lungs in the CM-sensitised group than in the GM- and HM-sensitised groups. CM-specific immunoglobulin (Ig) E, serum IgG1, and plasma histamine levels were also higher in CM-sensitised mice than in GM- or HM-sensitised mice. In addition, higher interleukin (IL) 4 and IL-17A levels and lower interferon-γ (IFN-γ) and IL-10 levels were observed in CM-sensitised mice compared with GM- and HM-sensitised mice, according to qPCR, indicating Th1/Th2 and Treg/Th17 imbalances. The CM-sensitised group had a higher proportion of IL-4- and IL-17A-producing CD3+ T cells but a lower proportion of IFN-γ- and IL-10-producing CD3+ T cells compared with the GM- and HM-sensitised groups, confirming the Th1/Th2 and Treg/Th17 imbalances. In conclusion, GM and HM were less allergenic than CM in mice as a result of a shift in the Th1/Th2 and Treg/Th17 imbalances; however, HM was less allergenic than GM and can be used as an alternative milk to develop infant formulas for children with CMA.
Collapse
Affiliation(s)
- Cuicui Duan
- Key Laboratory of Agro-products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun 130022, Jilin, People's Republic of China. and Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
| | - Lin Ma
- Key Laboratory of Agro-products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun 130022, Jilin, People's Republic of China.
| | - Lin Cai
- College of Food and Biology, Changchun Polytechnic, 3278 Weixing Road, Changchun 130033, Jilin, People's Republic of China
| | - Xiaolei Li
- Key Laboratory of Agro-products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun 130022, Jilin, People's Republic of China.
| | - Fumin Ma
- Key Laboratory of Agro-products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun 130022, Jilin, People's Republic of China.
| | - Junliang Chen
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan 471023, China
| | - Guicheng Huo
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
| | - Dan Li
- Key Laboratory of Agro-products Processing Technology, Jilin Provincial Department of Education, Changchun University, 6543 Weixing Road, Changchun 130022, Jilin, People's Republic of China.
| |
Collapse
|
48
|
Investigation of Basophil Activation Test for Diagnosing Milk and Egg Allergy in Younger Children. J Clin Med 2020; 9:jcm9123942. [PMID: 33291359 PMCID: PMC7762017 DOI: 10.3390/jcm9123942] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/26/2020] [Accepted: 12/03/2020] [Indexed: 01/28/2023] Open
Abstract
In children with concomitant food allergy and atopic dermatitis (AD), uncovering the causative food allergen is more arduous. We evaluated the basophil activation test (BAT) for its diagnostic value in children, including those with AD, for milk or egg allergy. We simultaneously measured serum-specific immunoglobulin E (sIgE) levels and performed BATs for cow’s milk and egg white. We compared their overall diagnostic performance using the area under the receiver operating characteristic curve (AUC) with the Delong method and compared them in children with AD. Analyses were completed for 75 children for milk allergy and for 85 children for egg allergy. The sIgE and percentage of basophils with the expression of CD63 were correlated for both milk (r = 0.384, p < 0.001) and egg (r = 0.557, p < 0.001). The AUC of sIgE (0.701) for milk allergy was significantly increased when combined with the BAT (0.805; p = 0.029). In children with AD, the AUC of the BAT (0.924) for milk allergy was significantly larger than that of sIgE (0.701; p = 0.017). The BAT is a potentially useful diagnostic tool for milk allergy in children when combined with sIgE. Moreover, it may be a surrogate marker for milk allergy in children with AD.
Collapse
|
49
|
Sun B, Feng D, Wang G, Yu X, Dong Z, Gao L. DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows' milk allergy in mouse model. Autoimmunity 2020; 53:467-475. [PMID: 33078976 DOI: 10.1080/08916934.2020.1836490] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Cows' milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow's milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitation in the knowledge of the pathological mechanism underlying CMA, however, the clinical interventions and therapies remain very unsatisfactory. AIM OF THE STUDY The transcriptional factor FOXP3 possesses crucial roles in CMA, and increased FOXP3 mRNA expression has a predictive function in faster acquisition of tolerance in infants with CMA. But the exact mechanism remains not fully elucidated. METHODS For PAG treatment, PAG (dissolved in saline 30 mg/mL, 0, 5, 10, 20 mg/kg BW) was administered daily intraperitoneally (ip) for one week at the time that 6 weeks after the CMP sensitisation. RESULTS In the present study, we revealed that the expression of FOXP3 is significantly up-regulated in PBMCs from CMA patients and CMA mice on mRNA and protein level. Furthermore, a dramatic reduction in the FOXP3 TSDR methylation and a significant increase in the expression of TET2 are observed in CMA patients and CMA mice. More importantly, we found that propargylglycine (PAG) significantly alleviates symptoms of CMA in mice by suppressing the expression of FOXP3 through restoring TET2 expression. CONCLUSIONS Our work revealed a novel function of PAG on CMA, which may provide a deeper insight into the pathomechanism of CMA and a novel therapy target for CMA clinical interventions.
Collapse
Affiliation(s)
- Beibei Sun
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| | - Dongjin Feng
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| | - Guangmeng Wang
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| | - Xiaohong Yu
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| | - Zhongmao Dong
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| | - Ling Gao
- Department of Gastroenterology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
50
|
Three Candidate Probiotic Strains Impact Gut Microbiota and Induce Anergy in Mice with Cow's Milk Allergy. Appl Environ Microbiol 2020; 86:AEM.01203-20. [PMID: 32826221 PMCID: PMC7580549 DOI: 10.1128/aem.01203-20] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/23/2020] [Indexed: 12/15/2022] Open
Abstract
We showed previously that three probiotic strains, i.e., Lactobacillus rhamnosus LA305, L. salivarius LA307, and Bifidobacterium longum subsp. infantis LA308, exerted different preventive effects in a mouse model of cow’s milk allergy. In this study, we evaluated their potential benefits in a curative mouse model of cow’s milk allergy. When administered for 3 weeks after the sensitization process and a first allergic reaction, none of the strains modified the levels of sensitization and allergic markers. However, all three strains affected gut bacterium communities and modified immune and inflammatory responses, leading to a tolerogenic profile. Interestingly, all three strains exerted a direct effect on dendritic cells, which are known to play a major role in food sensitization through their potentially tolerogenic properties and anergic responses. Taken together, these data indicate a potentially beneficial role of the probiotic strains tested in this model of cow’s milk allergy with regard to tolerance acquisition. Cow’s milk allergy is a worldwide public health issue, especially since there is no effective treatment, apart from milk and dairy product avoidance. The aim of this study was to assess the beneficial role of three probiotic strains previously selected for their prophylactic properties in a mouse model of β-lactoglobulin allergy. Administration of Lactobacillus rhamnosus LA305, L. salivarius LA307, or Bifidobacterium longum subsp. infantis LA308 for 3 weeks post–sensitization and challenge modified the composition of the gut microbiota, with an increase in the Prevotella NK3B31 group and a decrease in Marvinbryantia, belonging to the Lachnospiraceae family. Although no impact on markers of sensitization was detected, modifications of foxp3, tgfβ, and il10 ileal gene expression, as well as plasma metabolomic alterations in the tryptophan pathway, were observed. Moreover, ex vivo studies showed that all probiotic strains induced significant decreases in cytokine production by β-lactoglobulin-stimulated splenocytes. Taken together, these results suggest that the three probiotic strains tested lead to alterations in immune responses, i.e., induction of a tolerogenic anergy and anti-inflammatory responses. This anergy could be linked to cecal microbiota modifications, although no impact on fecal short-chain fatty acid (SCFA) concentrations was detected. Anergy could also be linked to a direct impact of probiotic strains on dendritic cells, since costimulatory molecule expression was decreased following coincubation of these strains with bone marrow-derived dendritic cells (BMDCs). To conclude, all three candidate probiotic strains induced strain-specific gut microbiota and metabolic changes, which could potentially be beneficial for general health, as well as anergy, which could contribute to oral tolerance acquisition. IMPORTANCE We showed previously that three probiotic strains, i.e., Lactobacillus rhamnosus LA305, L. salivarius LA307, and Bifidobacterium longum subsp. infantis LA308, exerted different preventive effects in a mouse model of cow’s milk allergy. In this study, we evaluated their potential benefits in a curative mouse model of cow’s milk allergy. When administered for 3 weeks after the sensitization process and a first allergic reaction, none of the strains modified the levels of sensitization and allergic markers. However, all three strains affected gut bacterium communities and modified immune and inflammatory responses, leading to a tolerogenic profile. Interestingly, all three strains exerted a direct effect on dendritic cells, which are known to play a major role in food sensitization through their potentially tolerogenic properties and anergic responses. Taken together, these data indicate a potentially beneficial role of the probiotic strains tested in this model of cow’s milk allergy with regard to tolerance acquisition.
Collapse
|