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Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals. Immunity 2022; 55:2454-2469.e6. [PMID: 36473469 DOI: 10.1016/j.immuni.2022.11.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 06/01/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022]
Abstract
Although food-directed immunoglobulin E (IgE) has been studied in the context of allergies, the prevalence and magnitude of IgG responses against dietary antigens are incompletely characterized in the general population. Here, we measured IgG binding against food and environmental antigens obtained from allergen databases and the immune epitope database (IEDB), represented in a phage displayed library of 58,233 peptides. By profiling blood samples of a large cohort representing the average adult Israeli population (n = 1,003), we showed that many food antigens elicited systemic IgG in up to 50% of individuals. Dietary intake of specific food protein correlated with antibody binding, suggesting that diet can shape the IgG epitope repertoire. Our work documents abundant systemic IgG responses against food antigens and provides a reference map of the exact immunogenic epitopes on a population scale, laying the foundation to unravel the role of food- and environmental antigen-directed antibody binding in disease contexts.
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Peruhova M, Mihova A, Altankova I, Velikova T. Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study. Antibodies (Basel) 2022; 11:23. [PMID: 35466276 PMCID: PMC9036216 DOI: 10.3390/antib11020023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 02/05/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS.
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Affiliation(s)
- Milena Peruhova
- Medical Faculty, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria;
| | - Antoaneta Mihova
- Laboratory of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria; (A.M.); (I.A.)
| | - Iskra Altankova
- Laboratory of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria; (A.M.); (I.A.)
| | - Tsvetelina Velikova
- Laboratory of Clinical Immunology, University Hospital Lozenetz, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria; (A.M.); (I.A.)
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3
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C3dg Quantification by PEG Precipitation and or TRIFMA. Methods Mol Biol 2021. [PMID: 33847929 DOI: 10.1007/978-1-0716-1016-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
Abstract
Detection of complement activation products can be carried out in a number of ways, and different methods are used in different laboratories. No international standard for measuring complement activation in the clinical setting has been agreed upon.Here we describe a modified assay for measuring C3dg. The assay is simple, inexpensive and stable. The estimation of C3dg directly reflects complement turnover independently of activation pathway.
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4
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Abstract
Irritable bowel syndrome (IBS) affects 10% to 15% of the population and often is difficult to treat with available pharmacologic agents. Dietary therapies for IBS are of particular interest because up to 90% of IBS patients exclude certain foods to improve their gastrointestinal symptoms. Among the available dietary interventions for IBS, the low FODMAP diet has the greatest evidence for efficacy. Although dietary therapies rapidly are becoming first-line treatment of IBS, gastroenterologists need to be aware of the negative effects of prescribing restrictive diets and red flag symptoms of maladaptive eating patterns.
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Zhang B, Liu E, Gertie JA, Joseph J, Xu L, Pinker EY, Waizman DA, Catanzaro J, Hamza KH, Lahl K, Gowthaman U, Eisenbarth SC. Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization. Sci Immunol 2020; 5:5/47/eaay2754. [PMID: 32385053 DOI: 10.1126/sciimmunol.aay2754] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 03/24/2020] [Indexed: 12/14/2022]
Abstract
Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and CD40L, it was T follicular helper (TFH) cell, germinal center, and T follicular regulatory (TFR) cell-independent. In contrast, IgG1 and IgE production to peanut required TFH cells. These data suggest an alternative paradigm in which the cellular mechanism of IgA production to food antigens is distinct from IgE and IgG1. We developed an equivalent assay to study this process in stool samples from healthy, nonallergic humans, which revealed substantial levels of peanut-specific IgA that were stable over time. Similar to mice, patients with loss of CD40L function had impaired titers of gut peanut-specific IgA. This work challenges two widely believed but untested paradigms about antibody production to dietary antigens: (i) the steady state/tolerogenic response to food antigens includes IgA production and (ii) TFH cells drive food-specific gut IgA.
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Affiliation(s)
- Biyan Zhang
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Elise Liu
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA.,Section of Rheumatology, Allergy and Immunology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Jake A Gertie
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Julie Joseph
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Lan Xu
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Elisha Y Pinker
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Columbia University, New York, NY 10027, USA
| | - Daniel A Waizman
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Jason Catanzaro
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA.,Section of Pulmonology, Allergy, Immunology and Sleep Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Kedir Hussen Hamza
- Department for Experimental Medicine, Immunology Section, Lund University, Lund 221 84, Sweden
| | - Katharina Lahl
- Department for Experimental Medicine, Immunology Section, Lund University, Lund 221 84, Sweden.,Division of Biopharma, Institute for Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
| | - Uthaman Gowthaman
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA
| | - Stephanie C Eisenbarth
- Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA. .,Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA.,Section of Rheumatology, Allergy and Immunology, Yale University School of Medicine, New Haven, CT, 06520, USA
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6
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Patil SU, Bunyavanich S, Cecilia Berin M. Emerging Food Allergy Biomarkers. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2020; 8:2516-2524. [PMID: 32888527 PMCID: PMC7479640 DOI: 10.1016/j.jaip.2020.04.054] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/17/2020] [Accepted: 04/18/2020] [Indexed: 12/12/2022]
Abstract
The management of food allergy is complicated by the lack of highly predictive biomarkers for diagnosis and prediction of disease course. The measurement of food-specific IgE is a useful tool together with clinical history but is an imprecise predictor of clinical reactivity. The gold standard for diagnosis and clinical research is a double-blind placebo-controlled food challenge. Improvement in our understanding of immune mechanisms of disease, development of high-throughput technologies, and advances in bioinformatics have yielded a number of promising new biomarkers of food allergy. In this review, we will discuss advances in immunoglobulin measurements, the utility of the basophil activation test, T-cell profiling, and the use of -omic technologies (transcriptome, epigenome, microbiome, and metabolome) as biomarker tools in food allergy.
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Affiliation(s)
- Sarita U. Patil
- Food Allergy Center, Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114
- Center for Immunological and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114
| | - Supinda Bunyavanich
- Jaffe Food Allergy Institute, Department of Pediatrics; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029
| | - M. Cecilia Berin
- Jaffe Food Allergy Institute, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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7
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Wang HY, Li Y, Li JJ, Jiao CH, Zhao XJ, Li XT, Lu MJ, Mao XQ, Zhang HJ. Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease. World J Clin Cases 2019; 7:2189-2203. [PMID: 31531314 PMCID: PMC6718778 DOI: 10.12998/wjcc.v7.i16.2189] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/21/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear.
AIM To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD.
METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn’s disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression.
RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831).
CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.
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Affiliation(s)
- Hai-Yang Wang
- Department of Gastroenterology, The Affiliated Sir Run Run Hospital, Nanjing Medical University, Nanjing 211100, Jiangsu Province, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yi Li
- Department of Gastroenterology, The Affiliated Sir Run Run Hospital, Nanjing Medical University, Nanjing 211100, Jiangsu Province, China
| | - Jia-Jia Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Chun-Hua Jiao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xiao-Jing Zhao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xue-Ting Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Mei-Jiao Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xia-Qiong Mao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Hong-Jie Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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8
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Järvinen KM, Martin H, Oyoshi MK. Immunomodulatory effects of breast milk on food allergy. Ann Allergy Asthma Immunol 2019; 123:133-143. [PMID: 31048004 PMCID: PMC6693634 DOI: 10.1016/j.anai.2019.04.022] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 04/23/2019] [Accepted: 04/23/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To summarize the literature on immunomodulatory effects of breast milk on sensitization and possible mechanisms of action. DATA SOURCES Animal and human studies in PubMed that assessed breastfeeding or breast milk composition in food allergy. STUDY SELECTIONS All recent studies and some older key publications focusing on this topic. RESULTS Human milk composition is highly variable among mothers, which can affect the developing infant immune system. Human milk also affects the infant gut microbiome, which is associated with food allergy. High levels of human milk immune factors (IgA, cytokines, oligosaccharides) are associated with reduced risk of food allergy in the infant; it remains uncertain whether these are directly protective or biomarkers of transferred protection. Animal studies highlight potential mechanisms of protection provided by antigens, transforming growth factor β, and immunocomplexes, yet their relevance is poorly understood in humans. The role of food antigens in human milk in initial sensitization or tolerance induction is unclear. CONCLUSION The protection against allergy development provided by human milk may be attributable to the effect on the infant gut microbiome or direct effects on immune system. Studies evaluating the effect of breastfeeding and human milk composition on food allergy are needed.
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Affiliation(s)
- Kirsi M Järvinen
- Division of Pediatric Allergy and Immunology & Center for Food Allergy, University of Rochester School of Medicine and Dentistry, Rochester, New York.
| | - Hayley Martin
- Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, New York
| | - Michiko K Oyoshi
- Division of Immunology, Boston Children's Hospital and the Departments of Pediatrics, Harvard Medical School, Boston, Massachusetts
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9
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Abstract
Oral tolerance is a state of systemic unresponsiveness that is the default response to food antigens in the gastrointestinal tract, although immune tolerance can also be induced by other routes, such as the skin or inhalation. Antigen can be acquired directly by intestinal phagocytes, or pass through enterocytes or goblet cell-associated passages prior to capture by dendritic cells (DCs) in the lamina propria. Mucin from goblet cells acts on DCs to render them more tolerogenic. A subset of regulatory DCs expressing CD103 is responsible for delivery of antigen to the draining lymph node and induction of Tregs. These DCs also imprint gastrointestinal homing capacity, allowing the recently primed Tregs to home back to the lamina propria where they interact with macrophages that produce IL-10 and expand. Tregs induced by dietary antigen include Foxp3+ Tregs and Foxp3- Tregs. In addition to Tregs, T cell anergy can also contribute to oral tolerance. The microbiota plays a key role in the development of oral tolerance, through regulation of macrophages and innate lymphoid cells that contribute to the regulatory phenotype of gastrointestinal dendritic cells. Absence of microbiota is associated with a susceptibility to food allergy, while presence of Clostridia strains can suppress development of food allergy through enhancement of Tregs and intestinal barrier function. It is not clear if feeding of antigens can also induce true immune tolerance after a memory immune response has been generated, but mechanistic studies of oral immunotherapy trials demonstrate shared pathways in oral tolerance and oral immunotherapy, with a role for Tregs and anergy. An important role for IgA and IgG antibodies in development of immune tolerance is also supported by studies of oral tolerance in humans. The elucidation of key pathways in oral tolerance could identify new strategies to increase efficacy of immunotherapy treatments for food allergy.
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Affiliation(s)
- Leticia Tordesillas
- Jaffe Food Allergy Institute, Immunology Institute, Mindich Child Health Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Cecilia Berin
- Jaffe Food Allergy Institute, Immunology Institute, Mindich Child Health Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Pediatrics, Icahn School of Medicine at Mount Sinai, Box 1198, One Gustave L. Levy Place, New York, NY, 10029, USA.
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10
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Epitope identification of specific naturally occurring human anti-avidin antibodies. Immunol Lett 2018; 196:119-123. [DOI: 10.1016/j.imlet.2017.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 11/21/2017] [Indexed: 11/20/2022]
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11
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Ohsaki A, Venturelli N, Buccigrosso TM, Osganian SK, Lee J, Blumberg RS, Oyoshi MK. Maternal IgG immune complexes induce food allergen-specific tolerance in offspring. J Exp Med 2017; 215:91-113. [PMID: 29158374 PMCID: PMC5748859 DOI: 10.1084/jem.20171163] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 08/24/2017] [Accepted: 09/28/2017] [Indexed: 12/17/2022] Open
Abstract
The role of maternal immune responses in tolerance induction is poorly understood. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)-dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring. Breastfeeding by OVA-sensitized mothers or maternal supplementation with IgG-IC was sufficient to induce neonatal tolerance. FcRn-dependent antigen presentation by CD11c+ dendritic cells (DCs) in offspring was required for oral tolerance. Human breast milk containing OVA-IgG-IC induced tolerance in humanized FcRn mice. Collectively, we demonstrate that interactions of maternal IgG-IC and offspring FcRn are critical for induction of T reg cell responses and control of food-specific tolerance in neonates.
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Affiliation(s)
- Asa Ohsaki
- Division of Immunology, Boston Children's Hospital, Boston, MA
| | | | | | | | - John Lee
- Division of Immunology, Boston Children's Hospital, Boston, MA.,Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Richard S Blumberg
- Gastroenterology Division, Brigham and Women's Hospital, Boston, MA.,Department of Medicine, Harvard Medical School, Boston, MA.,Harvard Digestive Diseases Center, Boston, MA
| | - Michiko K Oyoshi
- Division of Immunology, Boston Children's Hospital, Boston, MA .,Department of Pediatrics, Harvard Medical School, Boston, MA
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Mansueto P, D’Alcamo A, Seidita A, Carroccio A. Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity. World J Gastroenterol 2015; 21:7089-109. [PMID: 26109796 PMCID: PMC4476871 DOI: 10.3748/wjg.v21.i23.7089] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 04/04/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.
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13
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Cai C, Shen J, Zhao D, Qiao Y, Xu A, Jin S, Ran Z, Zheng Q. Serological investigation of food specific immunoglobulin G antibodies in patients with inflammatory bowel diseases. PLoS One 2014; 9:e112154. [PMID: 25393003 PMCID: PMC4230978 DOI: 10.1371/journal.pone.0112154] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Accepted: 10/13/2014] [Indexed: 12/13/2022] Open
Abstract
Objective Dietary factors have been indicated to influence the pathogenesis and nature course of inflammatory bowel diseases (IBD) with their wide variances. The aim of the study was to assess the prevalence and clinical significance of 14 serum food specific immunoglobulin G (sIgG) antibodies in patients with IBD. Methods This retrospective study comprised a total of 112 patients with IBD, including 79 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). Medical records, clinical data and laboratory results were collected for analysis. Serum IgG antibodies against 14 unique food allergens were detected by semi-quantitative enzyme linked immunosorbent assay (ELISA). Results Food sIgG antibodies were detected in 75.9% (60/79) of CD patients, 63.6% (21/33) of UC patients and 33.1% (88/266) of healthy controls (HC). IBD patients showed the significantly higher antibodies prevalence than healthy controls (CD vs. HC, P = 0.000; UC vs. HC, P = 0.001). However no marked difference was observed between CD and UC groups (P = 0.184). More subjects were found with sensitivity to multiple antigens (≥3) in IBD than in HC group (33.9% vs.0.8%, P = 0.000). Egg was the most prevalent food allergen. There was a remarkable difference in the levels of general serum IgM (P = 0.045) and IgG (P = 0.041) between patients with positive and negative sIgG antibodies. Patients with multiple positive allergens (≥3) were especially found with significant higher total IgG levels compared with sIgG-negative patients (P = 0.003). Age was suggested as a protective factor against the occurrence of sIgG antibodies (P = 0.002). Conclusions The study demonstrates a high prevalence of serum IgG antibodies to specific food allergens in patients with IBD. sIgG antibodies may potentially indicate disease status in clinical and be utilized to guide diets for patients.
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Affiliation(s)
- Chenwen Cai
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Jun Shen
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Di Zhao
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Yuqi Qiao
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Antao Xu
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Shuang Jin
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Zhihua Ran
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
| | - Qing Zheng
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China
- * E-mail:
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A simple set of validation steps identifies and removes false results in a sandwich enzyme-linked immunosorbent assay caused by anti-animal IgG antibodies in plasma from arthritis patients. SPRINGERPLUS 2013; 2:263. [PMID: 23875127 PMCID: PMC3695686 DOI: 10.1186/2193-1801-2-263] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Accepted: 06/11/2013] [Indexed: 12/20/2022]
Abstract
Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are chronic diseases characterized by activation of the immune system and production of antibodies. Thus, rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies in plasma samples from arthritis patients can interfere with immunoassays such as sandwich enzyme-linked immunosorbent assay (ELISA) systems often used in arthritis research. However, standard methodologies on how to test for false results caused by these antibodies are lacking. The objective of this study was to design a simple set of steps to validate a sandwich ELISA before using it for measuring analytes in plasma from arthritis patients. An interleukin-24 (IL-24) sandwich ELISA system was prepared with a monoclonal mouse capture antibody and a polyclonal goat detection antibody and tested for interference by rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies. Plasma samples from 23 patients with RA and SpA were used. No differences were found between plasma samples measured in wells coated with anti-IL-24 specific antibody and in wells coated with isotype control antibody (false positive results), and recombinant human IL-24 was not recovered in spiked samples (false negative results). This interference was removed after preincubating the plasma samples from patients with arthritis with goat or bovine IgG, suggesting that anti-animal IgG antibodies found in the plasma of the arthritis patients caused the false results. Additional testing showed that the signal-to-noise ratio could be increased by titration of the capture and detection antibodies and by using the ELAST amplification system. Finally, the calculated concentration of IL-24 was increased in ethylenediaminetetraacetic acid (EDTA) plasma compared to heparin plasma and serum and decreased with repetitive freeze/thaw cycles of the samples illustrating how sample handling could additionally contribute to the variations reported by different laboratories in measurement of the same analyte. This study proposes a simple set of validation steps to evaluate and optimize a sandwich ELISA before using it for measuring analytes in plasma from arthritis patients. Anti-animal IgG antibodies are also present in healthy individuals, suggesting that validation of ELISA systems for measuring non-arthritis samples could also be improved by this simple set of validation steps.
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Abstract
In the US and other developed countries, food allergy is a growing epidemic in pediatric populations with a substantial impact on health-related quality of life. As such, there are great efforts underway to unravel the mechanisms of oral mucosal tolerance and to better define the factors related to host and allergen exposure that contribute to the aberrant immune response leading to sensitization and clinical food allergy. Although more research is needed to eventually develop targeted treatment and prevention strategies, this review highlights our current understanding of the pathogenesis of IgE-mediated food allergy.
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Lewis JE, Lopez J, Ganuza A, Woolger JM, Chen L, Melillo AB, Alonso Y, Rafatjah S, Konefal J, Sarabia A, Leonard SM, Long EG, Tiozzo E. A pilot study eliminating immunologically-reactive foods from the diet and its effect on symptomatology and quality of life in persons with chronic migraines and headaches. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/ojim.2013.31003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Berin MC. Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin Immunopathol 2012; 34:633-42. [PMID: 22777546 DOI: 10.1007/s00281-012-0325-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Accepted: 06/20/2012] [Indexed: 01/01/2023]
Abstract
The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens.
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Affiliation(s)
- M Cecilia Berin
- Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
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Assay interference caused by antibodies reacting with rat kappa light-chain in human sera. J Immunol Methods 2011; 372:204-8. [PMID: 21771595 DOI: 10.1016/j.jim.2011.06.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Accepted: 06/24/2011] [Indexed: 11/21/2022]
Abstract
The enzyme-linked immunosorbent assay (ELISA) and its derivatives are powerful tools used in research, in the clinic, and in many other analytical and quality control settings. In general, ELISAs are robust, reproducible and reliable. However, a number of pitfalls of ELISAs have been described over the years. The issue of rheumatoid factor (RF), autoantibodies against the Fc portion of IgG, is well recognized (yet often forgotten), as are problems arising from heterophilic antibodies induced by external antigens that cross-react with self-antigens. A few years ago focus was on human anti-mouse antibodies (HAMA) concomitant with the increased use of mouse monoclonal antibody therapy, a problem that is now diminishing due to development of humanized antibodies. Issues pertaining to food antigens or environmentally encountered antigens are less recognized. We report a recently encountered example of the latter resulting in interference in a solid-phase sandwich assay. Due to the set-up employing a monoclonal rat IgG for capture and a monoclonal rat IgM for development the interference had to be human antibodies reacting with rat light-chain. Out of 102 Danish Caucasian blood donors we found a prevalence of anti-rat kappa light chain antibodies of close to 40% (39/102, defined as at least 2-fold elevated measurements), with around 6% (6/102) having very high levels (defined as at least 4-fold elevated measurements), yielding significantly higher measurements in the assay designed to measure the complement component MAp19 in serum samples. The interference could be blocked by the addition of rat immunoglobulin to the sample buffer. An individual, who had been followed over time, demonstrated a periodic increase of interfering antibodies, highlighting that it is an independently varying parameter and thereby a variable interference in assays. Our results highlight a major pitfall of potential relevance to many sandwich-type assays, as well as an approach to rectify such problems.
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Abstract
In this article we review the pathophysiology of food allergy, which affects 4% of US children and 2% of adults, and is increasing in prevalence. Most food allergens share certain specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. During allergic sensitization, these allergens are encountered by specialized dendritic cell populations in the gut, which leads to T-cell priming and the production of allergen-specific IgE production by B cells. Tissue-resident mast cells then bind IgE, and allergic reactions are elicited when mast cells are reexposed to allergen. Adjacent IgE molecules bound to the surface of the mast cell become cross-linked, causing mast cell degranulation and release of powerful vasoactive compounds that cause allergic symptoms.
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Affiliation(s)
- Brian P Vickery
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Box 2644, Durham, NC 27710, USA.
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Degn SE, Jensen L, Gál P, Dobó J, Holmvad SH, Jensenius JC, Thiel S. Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene involved in regulation of the complement system. J Immunol Methods 2010; 361:37-50. [PMID: 20673767 DOI: 10.1016/j.jim.2010.07.006] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2010] [Revised: 07/19/2010] [Accepted: 07/20/2010] [Indexed: 11/24/2022]
Abstract
The lectin pathway of complement is part of the innate immune system. The complement-activating pattern-recognition molecules (for which we suggest the abbreviation CAPREMs) mannan-binding lectin (MBL) and the three ficolins (H-, L- and M-ficolin) circulate in complexes with MBL-associated serine proteases (MASP-1, -2 and -3) and two additional proteins (MAp19 and MAp44, also termed sMAP and MAP-1, respectively). When MBL or ficolins recognize a microorganism or altered self components, activation of the MASPs ensues, leading to the activation of the complement system. MASP-1, MASP-3 and MAp44 are all three encoded by the MASP1 gene. MASP-1 and -3 share five domains (constituting the so-called A-chain), but have unique protease domains (B-chains). MAp44 shares the first four domains with MASP-1 and MASP-3, followed by 17 unique C-terminal amino acid residues. Thus, assays for the protease domain of MASP-3 and for the 17 C-terminal amino acids of MAp44 are required to measure these proteins specifically and here we present such assays for MASP-3 and MAp44. MASP-3 was captured with a monoclonal antibody (5F5) reacting with a common domain of the three proteins (CCP1) and the assay was developed with a monoclonal antibody (38.12.3) specific for the C-terminal part of the MASP-3 protease domain. MAp44 was captured with a monoclonal antibody (2D5) reacting with the C-terminus of MAp44 followed by assay development with a monoclonal anti-CCP1 antibody (4H2). Using Superose 6 gel permeation chromatography of serum, MASP-3 and MAp44 were found in complexes, which eluted in positions corresponding to 600-800 kDa and 500-700 kDa, respectively. The level of MASP-3 in donor sera (N=200) was log-normally distributed with a median value of 5.0 μg/ml (range: 1.8-10.6 μg/ml), and the corresponding value for MAp44, also log-normally distributed, was 1.7 μg/ml (range: 0.8-3.2 μg/ml). For MASP-3, the inter-assay coefficients of variation of low, intermediate and high level internal controls were 4.9%, 6.9% and 3.9% (N=12). For MAp44, the corresponding inter-assay CVs were 7.6%, 6.2%, and 7.0% (N=12). MASP-3 levels were low at birth and reached adult levels within the first 6 months, whereas MAp44 levels fell slightly during the first 6 months. Concomitant with the acute phase response in patients undergoing major surgery, levels of both proteins fell slightly over 1-2 days, but whereas MASP-3 recovered to baseline values over another 2 days, MAp44 only reached baseline values at around day 30. Thus, neither of the two proteins behaves as a classical acute phase protein.
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Affiliation(s)
- Søren E Degn
- Department of Medical Microbiology and Immunology, Aarhus University, Wilhelm Meyers Allé 4, 8000 Arhus C, Denmark.
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Verhasselt V. Oral tolerance in neonates: from basics to potential prevention of allergic disease. Mucosal Immunol 2010; 3:326-33. [PMID: 20485330 DOI: 10.1038/mi.2010.25] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the last two cases, the diseases develop early in life, stressing the necessity of understanding how oral tolerance is set up in neonates. This article reviews the parameters that have been outlined in adult animal models as necessary for tolerance induction and assesses whether these factors operate in neonates. In addition, we highlight the factors that are specific for this period of life and discuss how they could have an impact on oral tolerance. We pay particular attention to maternal influence on early oral tolerance induction through breast-feeding and outline the major parameters that could be modified to optimize tolerance induction in early life and possibly prevent allergic diseases.
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22
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Morris ER, Hampton SM, Morgan JB. Serum antibody levels to three food antigens in a topic and non-a topic subjects. Int J Food Sci Nutr 2009. [DOI: 10.3109/09637489209027526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Volpi N, Maccari F. Serum IgG Responses to Food Antigens in the Italian Population Evaluated by Highly Sensitive and Specific ELISA Test. J Immunoassay Immunochem 2008; 30:51-69. [DOI: 10.1080/15321810802571903] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Abstract
Functional gastrointestinal disorders (FGIDs) commonly affect children and are associated with short- and long-term morbidity. Although the pathogenesis of pain-related FGIDs remains incompletely understood, most investigators agree on a multifactorial etiology and the presence of an altered brain-gut interaction. A continuous interplay of genetic and environmental factors appears to shape the development of the central and enteric nervous systems. The biopsychosocial model is the current operational framework for children with FGIDs, as it recognizes the interaction between social and environmental influences and psychological and physiologic processes. The biopsychosocial model proposes that specific permutations of genetic susceptibility, early life experiences, sociocultural issues, and coping mechanisms could explain the variability in clinical presentation and outcome among individuals.
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Affiliation(s)
- Ashis V Barad
- Children's Memorial Hospital, Northwestern University, 700 West Fullerton Avenue, Box 57, Chicago, IL 60614, USA.
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25
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Crevel RWR, Cooper KJ, Poulsen LK, Hummelshoj L, Bindslev-Jensen C, Burks AW, Sampson HA. Lack of immunogenicity of ice structuring protein type III HPLC12 preparation administered by the oral route to human volunteers. Food Chem Toxicol 2006; 45:79-87. [PMID: 17027137 DOI: 10.1016/j.fct.2006.07.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2005] [Revised: 06/27/2006] [Accepted: 07/18/2006] [Indexed: 11/16/2022]
Abstract
Before a novel protein can be used in foods, its potential allergenicity must be assessed. In this study, healthy volunteers consumed ice structuring protein (ISP) Type III preparation or a control material 5 days a week for a total of 8 weeks. General measures of health were recorded during the study, and the immunogenicity of the protein was assessed by monitoring the levels of IgG and IgE antibodies specific for ISP Type III. The participants remained in good health throughout the study and during the 4 week follow-up period. No IgG or IgE antibodies specific for ISP Type III were detected in the blood of the participants. Investigations of immunogenicity in man have not been previously applied in the context of safety evaluation and they do not form part of the regimens proposed for the evaluation of protein allergenicity. Consequently no standardised protocols exist for such studies, nor any background against which to interpret the results. Nevertheless, the absence of an immune response using a protocol which could have been expected to result in a response with a strongly immunogenic protein, confirms the conclusions of earlier published work, and attests to the lack of allergenicity of ISP Type III preparation.
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Affiliation(s)
- R W R Crevel
- Safety and Environmental Assurance Centre, Sharnbrook, Unilever Colworth, Bedford MK44 1LQ, UK, and Allergy Center, Odense University Hospital, Denmark.
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26
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Park MI, Camilleri M. Is there a role of food allergy in irritable bowel syndrome and functional dyspepsia? A systematic review. Neurogastroenterol Motil 2006; 18:595-607. [PMID: 16918724 DOI: 10.1111/j.1365-2982.2005.00745.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A significant proportion of adults believe they suffer from food allergy, and 20-65% of patients with irritable bowel syndrome (IBS) attribute their symptoms to something in food that activates an abnormal response. This systematic review evaluates the role of food allergy in aetiology and management of these disorders. Activation of gastrointestinal mucosal immune system may be one of the causative factors in the pathogenesis of functional dyspepsia and IBS. This activation may result from effects of bacterial infection or other luminal factors including commensal microbial flora and food antigens. Some studies have reported on the role of food allergy in IBS; only one epidemiological study on functional dyspepsia and food allergy has been published. The mechanism by which food activates mucosal immune system is uncertain, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients. Further well-controlled studies are needed to establish whether food allergy plays a role in the pathophysiology of functional dyspepsia and IBS.
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Affiliation(s)
- M-I Park
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Group, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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27
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Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol 2005; 100:1550-7. [PMID: 15984980 DOI: 10.1111/j.1572-0241.2005.41348.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Food hypersensitivity is a common perception among irritable bowel syndrome (IBS) patients. Data from dietary elimination and food challenge studies support an etiopathological role of diet in IBS, but there are no well-established tests to identify food hypersensitivity. AIM To compare IgG4 and IgE titers to common food antigens in IBS and controls. METHOD One hundred and eight IBS [52 diarrhea-predominant (D-IBS); 32 constipation-predominant (C-IBS); 24 alternating (Alt-IBS)], and 43 controls were included in the study. IgG4 and IgE titers and skin prick testing (SPT) to 16 common foods including milk, eggs, cheese, wheat, rice, potatoes, chicken, beef, pork, lamb, fish, shrimps, soya bean, yeast, tomatoes, and peanuts were measured. RESULTS IBS had significantly higher IgG4 titers (mug/L) to wheat (395 IQR +/- 1,011 vs 0 IQR +/- 285, p < 0.001), beef (1,079 IQR +/- 930 vs 617 IQR +/- 435, p < 0.001), pork (481 IQR +/- 379 vs 258 IQR +/- 496, p < 0.001), and lamb (241 IQR +/- 460 vs 167 IQR +/- 232, p= 0.009) compared to controls. These differences were maintained across all three subgroups. The antibody titers to potatoes, rice, fish, chicken, yeast, tomato, and shrimps were not significantly different. No significant difference in IgE titers was observed between IBS and controls. SPT was positive for only a single antigen in 5 of 56 patients tested with the same panel of foods. No correlation was seen between the pattern of elevated IgG4 antibody titers and patients' symptoms. CONCLUSION Serum IgG4 antibodies to common foods like wheat, beef, pork, and lamb are elevated in IBS patients. In keeping with the observation in other atopic conditions, this finding suggests the possibility of a similar pathophysiological role for IgG4 antibodies in IBS.
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Affiliation(s)
- Sameer Zar
- OGEM Department, St Georges Hospital Medical School, Blackshaw Road, London, UK
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28
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Christensen HR, Larsen LC, Frøkiaer H. The oral immunogenicity of BioProtein, a bacterial single-cell protein, is affected by its particulate nature. Br J Nutr 2003; 90:169-78. [PMID: 12844389 DOI: 10.1079/bjn2003863] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The bacterial single-cell protein BioProtein (BP; Norferm Danmark, Odense, Denmark), produced by fermentation of natural gas with methanotrophic bacteria, is a potential protein source for man and animals. For human consumption, removal of the nucleic acid is necessary. Preliminary studies have shown that ingested BP induces a specific immune response. The objective of the present study was to characterize the type of response, its development over time and product-related causative factors. Mice were fed with diets containing 60 g nucleic acid-reduced BP/kg, 240 g nucleic acid-reduced BP/kg, 240 g untreated BP (basic BP)/kg or 240 g casein/kg (control). In another study, mice were fed 240 g basic BP/kg, whole cell-free BP-culture homogenate or control diet. The immune response was monitored using an ELISA for BP-specific immunoglobulin in blood and BP-specific immunoglobulin A in blood and saliva. Ingested BP induced a steady specific mucosal and systemic immune response, characterized by a dose-dependent production of immunoglobulin and immunoglobulin A in blood and immunoglobulin A in saliva. Basic BP and nucleic acid-reduced BP induced identical responses. However, feeding mice BP-culture homogenate induced immunoglobulin A in saliva but there was no systemic response. The antibodies from BP-fed mice cross-reacted with BP-culture homogenate revealing the presence of the same antigenic components in the two products despite the different oral immunogenicity. Thus, ingestion of BP induces a persistent mucosal and systemic immune response of which the systemic response can be avoided by ingesting a BP preparation free of whole cells. This indicates the importance of the non-particulate constitution of single-cell protein products intended for human or animal consumption.
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Affiliation(s)
- Hanne R Christensen
- BioCentrum-DTU, Section for Biochemistry and Nutrition, Technical University of Denmark, DK-2800 Lyngby, Denmark.
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Abstract
Irritable bowel syndrome is a common condition but its pathophysiology remains poorly understood. Many irritable bowel syndrome patients give a history of food intolerance, but data from dietary elimination and re-challenge studies are inconclusive. Multiple aetio-pathological mechanisms have been postulated. The gut has an extensive immune system but current understanding of processing of food antigens in health and disease is limited. There is no clinically useful marker available to test for food hypersensitivity in irritable bowel syndrome. Researchers have employed both skin tests and serum immunoglobulins (IgG and IgE) as markers of food hypersensitivity in various disorders including irritable bowel syndrome, but published data are equivocal. In this article, the evidence for the role of food hypersensitivity in irritable bowel syndrome is reviewed and, based on the available data, a possible pathophysiological hypothesis has been formulated.
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Affiliation(s)
- S Zar
- Department of General Surgery, St George's Hospital Medical School, London, UK
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Abstract
This is a short review of the literature with a bias toward the author's work. Small amounts of dietary antigens are taken up into the circulation. B-cell responses to foods (antibodies and antibody-secreting cells) occur as a physiological event locally and in the circulation in all three major immunoglobulin classes. A low levels of IgE is also a normal phenomenon. IgA anti-gliadin antibodies represent an exception. Antibody titers in general tend to decline with age. T-cell responses specific for foods are low in the circulation of healthy subjects. T-cell cytokines are more frequently produced in the gastrointestinal mucosa compared with the circulation. Results indicate that the phenomenon of oral tolerance takes place in humans. Oral tolerance within the T cell system may represent an important regulatory mechanism for normal immunity.
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Affiliation(s)
- S Husby
- Department of Pediatrics, Odense University Hospital, Denmark
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Tchernychev B, Rabinkov A, Miron T, Wilchek M. Natural antibodies against alliinase in human serum and polyclonal antibodies elicited in rabbit share the same immunogenic determinants. Immunol Lett 2000; 71:43-7. [PMID: 10709784 DOI: 10.1016/s0165-2478(99)00162-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Human serum contains natural antibodies against alliinase, a protein abundantly found in garlic (Allium sativum) cloves. In order to study the epitope(s) of this protein recognized by anti-alliinase antibodies, we used a random hexapeptide library displayed on filamentous M13 phage. Analysis of the phagotopes selected on rabbit anti-alliinase antibodies revealed that the motif-GKXVXX- was common for all peptides. The most frequent phage displaying -GKHVAV- sequence has a 50% identity with the original alliinase sequence (amino acid residues 156-161). The position of this epitope is only nine amino acids apart from the oligosaccharide chain attached to the N146. The rabbit anti-alliinase immunoglobulin G (IgG), which bound the phages displaying this phagotope, also bound the corresponding peptide derived from the alliinase sequence. Affinity-purified natural antibodies against alliinase, present in normal human serum (which can specifically recognize the native and denaturated protein) also bound the selected phagotope. Thus, our results indicate that specific natural anti-dietary protein antibodies presented in human serum can have the same. or overlapping. epitopes with the IgG evoked during the active (experimental) immunization in animals.
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Affiliation(s)
- B Tchernychev
- Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
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Affiliation(s)
- A M Faria
- Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
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Hirota K, Hashida S, Ishikawa E, Totani M. Sensitive enzyme immunoassay for anti-beta-lactoglobulin IgG in serum. Ann Clin Biochem 1998; 35 ( Pt 5):649-55. [PMID: 9768332 DOI: 10.1177/000456329803500509] [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: 11/16/2022]
Abstract
A sensitive enzyme immunoassay for anti-beta-lactoglobulin immunoglobulin G (IgG) in serum is described. Serum containing anti-beta-lactoglobulin IgG was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-beta-lactoglobulin conjugate and beta-lactoglobulin-peroxidase conjugate. The complex formed from the three components was trapped onto polystyrene balls coated with anti-2,4-dinitrophenyl group IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with anti-human IgG.gamma-chain IgG. Bound peroxidase activity was determined by fluorometry. This enzyme immunoassay was 100- to 1000-fold more sensitive and more reliable than the enzyme-linked immunosorbent assay (ELISA). Anti-beta-lactoglobulin IgG was detected in 91% of healthy subjects using this method.
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Affiliation(s)
- K Hirota
- Division of Maternal and Child Health Science, National Institute of Health and Nutrition, Tokyo, Japan
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Saukkonen T, Savilahti E, Madácsy L, Arató A, Körner A, Barkai L, Sarnesto A, Akerblom HK. Increased frequency of IgM antibodies to cow's milk proteins in Hungarian children with newly diagnosed insulin-dependent diabetes mellitus. Eur J Pediatr 1996; 155:885-9. [PMID: 8891559 DOI: 10.1007/bf02282839] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
UNLABELLED We investigated the association between serum antibodies to cow's milk proteins and insulin-dependent diabetes mellitus (IDDM) in Hungarian children. Forty-eight children 1.0-17.1 years of age with newly diagnosed IDDM and 74 control children 1.0-16.0 years of age were studied for serum IgG, IgA and IgM antibodies to cow's milk, beta-lactoglobulin, bovine serum albumin and ovalbumin by enzyme-linked immunosorbent assays. The specificity of IgM antibodies to beta-lactoglobulin and bovine serum albumin was controlled by Western blot. The levels of IgG and IgA antibodies to cow's milk proteins were similar in children with and without IDDM, with the exception of slightly increased levels of IgA antibodies to beta-lactoglobulin in diabetic children (P = 0.05). The levels of IgM antibodies to cow's milk were significantly higher in IDDM patients than in control children (P = 0.0002). Children with IDDM more often had IgM antibodies to beta-lactoglobulin (46.3% vs 18.8%; P = 0.002) and bovine serum albumin (87.8% vs 49.3%, P < 0.0001) than control children. Neither the levels of IgG or IgA antibodies to ovalbumin nor the frequency of IgM antibodies to ovalbumin differed between diabetic and control children. CONCLUSION In Hungarian children, clinical manifestation of IDDM is often associated with IgM antibody response to cow's milk protein and its fractions, beta-lactoglobulin and bovine serum albumin, indicating a loss of immunological tolerance to these proteins. IgG and IgA antibodies to cow's milk proteins, associated with an early introduction of cow's milk in diet, seem to play a minor role in the development of childhood IDDM in Hungary.
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Affiliation(s)
- T Saukkonen
- Children's Hospital, University of Helsinki, Finland
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Saukkonen T, Savilahti E, Landin-Olsson M, Dahlquist G. IgA bovine serum albumin antibodies are increased in newly diagnosed patients with insulin-dependent diabetes mellitus, but the increase is not an independent risk factor for diabetes. Acta Paediatr 1995; 84:1258-61. [PMID: 8580622 DOI: 10.1111/j.1651-2227.1995.tb13544.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
We studied the significance of antibodies to bovine serum albumin (BSA) as a risk factor for insulin-dependent diabetes mellitus (IDDM) in a case-control setting. IgA and IgG antibodies to BSA and ovalbumin were measured from sera of 104 patients with newly diagnosed IDDM and of 111 matched controls by enzyme-linked immunosorbent assay. Patients with diabetes had significantly higher levels of IgA antibodies to BSA (p = 0.003); IgG antibodies also tended to be higher (p = 0.08). Levels of IgA antibodies to ovalbumin were similar in the patients and controls, but IgG antibodies were higher in controls (p = 0.02). When antibodies to BSA, beta-lactoglobulin, whole cow's milk and islet cell antibodies were studied as risk determinants of IDDM in a multivariate, logistic regression analysis, IgA antibodies to beta-lactoglobulin and to cow's milk were independently associated with the risk (p = 0.037 and 0.048, respectively), while antibodies to BSA were not a significant risk factor. The results question the role of BSA as a cross-reacting antigen with pancreatic beta-cell surface proteins in the aetiology of IDDM.
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Affiliation(s)
- T Saukkonen
- Children's Hospital, University of Helsinki, Finland
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Affiliation(s)
- R M Barnes
- Department of Immunology, Royal Liverpool University Hospital, UK
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Koskinen S, Hirvonen M, Tölö H. An enzyme immunoassay for the determination of anti-IgA antibodies using polyclonal human IgA. J Immunol Methods 1995; 179:51-8. [PMID: 7868924 DOI: 10.1016/0022-1759(94)00269-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
An enzyme immunoassay (EIA) for screening and quantitation of serum anti-IgA antibodies of IgG class is described. This method is based on the use of purified polyclonal human serum IgA as the coating antigen and a commercial alkaline phosphatase-conjugated anti-human IgG as the detecting antibody. Nonspecific reactions were minimized by blocking vacant protein binding sites with bovine serum albumin and by using individual sample blanks. The IgA specificity of a positive antibody finding was confirmed by testing inhibition: pooled normal human serum inhibited the binding of specific antibodies by over 80%. The same degree of inhibition could also be demonstrated by a commercial myeloma IgA preparation and by the IgA used for coating but not by IgA-deficient serum (< 0.05 mg/l). On the basis of the mean anti-IgA antibody titre in EIA, a value of 12,000 arbitrary units of anti-IgA per litre (AU/l) was assigned to a patient serum used as standard in the assay. Anti-IgA results obtained by EIA and haemagglutination correlated well, which makes it possible to compare earlier HA results with those obtained now by EIA. The measuring range of the assay was 0.6-27 AU/l and the lowest quantifiable concentration 7 AU/l. The dilution requirement for serum was 1/16. The interassay coefficients of variation for control sera with antibody levels from 35 AU/l to 3770 AU/l varied from 9 to 12%.
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Affiliation(s)
- S Koskinen
- Finnish Red Cross Blood Transfusion Service, Helsinki, Finland
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Virtanen SM, Saukkonen T, Savilahti E, Ylönen K, Räsänen L, Aro A, Knip M, Tuomilehto J, Akerblom HK. Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children. Childhood Diabetes in Finland Study Group. Diabetologia 1994; 37:381-7. [PMID: 8063039 DOI: 10.1007/s001250050121] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date- and sex-matched population-based control children in the nationwide "Childhood Diabetes in Finland" study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabetic-population-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.
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Affiliation(s)
- S M Virtanen
- Department of Applied Chemistry and Microbiology, University of Helsinki, Finland
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Uibo O, Uibo R, Kleimola V, Jõgi T, Mäki M. Serum IgA anti-gliadin antibodies in an adult population sample. High prevalence without celiac disease. Dig Dis Sci 1993; 38:2034-7. [PMID: 8223078 DOI: 10.1007/bf01297081] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
IgA-class anti-gliadin antibodies (AGA) and IgA-, IgG-, IgM-class anti-reticulin antibodies (ARA) were determined in 1461 persons, representing 84% of a population from the village of Karksi-Nuia. AGA were detected by enzyme-linked immunosorbent assay (ELISA) and ARA by indirect immunofluorescence. Fifty-two (3.5%) persons had IgA-class AGA, of whom 48 and an additional three of four persons with diarrhea were biopsied. All biopsies showed normal small intestinal mucosal architecture. All 1461 persons were negative for ARA. Our results demonstrate that AGA are frequently detected in an adult Estonian population and positivity increases with age in persons with normal small intestinal mucosa. Positivity for AGA does not predict silent undetected celiac disease but rather represents a normal response to dietary antigens in the elderly. Inability to detect ARA suggests that celiac disease does not exist in this population. As none of the AGA-positive but ARA-negative biopsied persons had celiac disease, ARA might be a more specific serologic marker for celiac disease than AGA.
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Affiliation(s)
- O Uibo
- Department of Pediatrics, University of Tartu, Estonia
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Karjalainen J, Martin JM, Knip M, Ilonen J, Robinson BH, Savilahti E, Akerblom HK, Dosch HM. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 1992; 327:302-7. [PMID: 1377788 DOI: 10.1056/nejm199207303270502] [Citation(s) in RCA: 301] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Cow's milk has been implicated as a possible trigger of the autoimmune response that destroys pancreatic beta cells in genetically susceptible hosts, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin (BSA) is the milk protein responsible, and an albumin peptide containing 17 amino acids (ABBOS) may be the reactive epitope. Antibodies to this peptide react with p69, a beta-cell surface protein that may represent the target antigen for milk-induced beta-cell--specific immunity. METHODS We used immunoassays and Western blot analysis to analyze anti-BSA antibodies in the serum of 142 children with insulin-dependent diabetes mellitus, 79 healthy children, and 300 adult blood donors. Anti-ABBOS antibodies were measured in 44 diabetic patients at the time of diagnosis, three to four months later, and one to two years later. RESULTS All the diabetic patients had elevated serum concentrations of IgG anti-BSA antibodies (but not of antibodies to other milk proteins), the bulk of which were specific for ABBOS: The mean (+/- SE) concentration was 8.5 +/- 0.2 kilofluorescence units (kfU) per microliter, as compared with 1.3 +/- 0.1 kfU per microliter in the healthy children. IgA antibodies were elevated as well, but not IgM antibodies. The antibody concentrations declined after diagnosis, reaching normal levels in most patients within one to two years. The initial decline involved anti-ABBOS--specific antibodies almost exclusively. Much lower serum concentrations of anti-BSA antibodies were found in all 379 control subjects, but only 2.5 percent of them had small amounts of ABBOS-specific IgG. CONCLUSIONS Patients with insulin-dependent diabetes mellitus have immunity to cow's-milk albumin, with antibodies to an albumin peptide that are capable of reacting with a beta-cell--specific surface protein. Such antibodies could participate in the development of islet dysfunction.
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Affiliation(s)
- J Karjalainen
- Hospital for Sick Children, Department of Pediatrics and Immunology, University of Toronto, ON, Canada
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Controversial Concepts and Techniques in the Diagnosis and Management of Food Allergies. Immunol Allergy Clin North Am 1991. [DOI: 10.1016/s0889-8561(22)00081-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Ruths S, Driedijk PC, Weening RS, Out TA. ELISA procedures for the measurement of IgG subclass antibodies to bacterial antigens. J Immunol Methods 1991; 140:67-78. [PMID: 2061615 DOI: 10.1016/0022-1759(91)90127-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We have developed enzyme-linked immunosorbent assays (ELISA) of IgG subclass antibodies against whole bacteria and bacterial antigens using enzyme-labelled mouse monoclonal antibodies. The properties of different anti-subclass antibodies were compared. In sera from 18 healthy adults we measured the IgG subclass distribution of specific antibodies against Staphylococcus aureus and Haemophilus influenzae b and against distinct bacterial components: pneumococcal capsular polysaccharides, dextran and tetanus toxoid. We found that antibodies against protein (tetanus toxoid) were mainly IgG1, with some contribution of IgG4 and IgG2. Antibodies against polysaccharides (pneumococcal PS and dextran) and whole bacteria were restricted mainly to IgG1 and IgG2.
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Affiliation(s)
- S Ruths
- Clinical Immunology Laboratory, Academic Medical Centre (AMC), Amsterdam, The Netherlands
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Abstract
Sera collected sequentially during a 24-month interval from 11 individuals with shrimp hypersensitivity and 10 nonhypersensitive control subjects were evaluated for shrimp-specific IgE, IgG, IgM, and IgA reactivity. Shrimp-hypersensitive subjects underwent double-blind, placebo-controlled shrimp challenges; seven exhibited positive challenges, and four subjects reported the subjective symptom of oropharyngeal pruritus. Shrimp-specific IgE levels in all subjects were relatively constant during the 24 months of this study and not affected by shrimp challenge, although some fluctuation in the shrimp-specific IgG, IgM, and IgA reactivity were noted, apparently unrelated to shrimp challenge. Shrimp-specific IgE and IgG, but not IgM and IgA, were significantly higher in the group with shrimp hypersensitivity as compared to the control subjects. Moreover, the challenge-positive subjects had higher levels of both shrimp-specific IgE and IgG than subjects reporting pruritus. The levels of shrimp-specific IgG correlated directly with shrimp-specific IgE reactivity. These studies indicate that serum levels of shrimp-specific IgE are significantly elevated in shrimp-hypersensitive subjects who exhibit positive food challenges, and these baseline levels did not appear to be altered long term by isolated shrimp challenge. Furthermore, baseline shrimp-specific antibody (IgG, IgM, and IgA) levels noted in normal subjects were not markedly affected by frequent ingestion of shrimp.
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Affiliation(s)
- C B Daul
- Department of Medicine, Alton Ochsner Medical Institutions, New Orleans, La
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Affiliation(s)
- I Quinti
- Allergy and Immunology Division, University La Sapienza, Rome, Italy
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QUINTI ISABELLA, PAGANELLI ROBERTO, SCALA ENRICO, GUERRA EMMA, AIUTI FERNANDO. Humoral response to food antigens. Allergy 1989. [DOI: 10.1111/j.1398-9995.1989.tb04318.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Kávai M, Rasmussen JM, Baatrup G, Zsindely A, Svehag SE. Inefficient binding of IgM immune complexes to erythrocyte C3b-C4b receptors (CR1) and weak incorporation of C3b-iC3b into the complexes. Scand J Immunol 1988; 28:123-8. [PMID: 2969612 DOI: 10.1111/j.1365-3083.1988.tb02423.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The binding of soluble complement-reacted IgM immune complexes (IC) to erythrocyte (E) C3b-C4b receptors (CR1) and the incorporation of C3b-iC3b into solid phase IgM-IC was investigated. The optimal binding of liquid phase IgM-IC to E-CR1 was obtained with IC formed at moderate antibody excess, but the binding was low (2-3%) when compared to the binding of the corresponding IgG-IC (50-60%). Solid phase IC were prepared by coating microwells with heat-aggregated bovine serum albumin (BSA) followed by incubation with rabbit IgM anti-BSA antibody. The IC were reacted with human serum at 37 degrees C. The binding of C3b-iC3b was determined by use of biotinylated F(ab')2 antibodies to C3b-C3c and avidin-coupled alkaline phosphatase. The incorporation of C3b-iC3b into solid-phase IgM-IC increased when increasing amounts of IgM antibody were reacted with the antigen. The binding reaction was slow, reaching a maximum after about 2 h at 37 degrees C. The binding of C3b-iC3b to the IgM-IC was remarkably inefficient when compared to the incorporation into IgG-IC reacted with the same amounts of BSA-precipitating antibody.
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Affiliation(s)
- M Kávai
- Third Department of Medicine, University Medical School, Debrecen, Hungary
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48
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Sheffer AL, Lieberman PL, Aaronson DW, Anderson JA, Kaplan AP, Pierson WE, Ellis EF, Lichtenstein LM, Lockey RF, Salvaggio JE. Measurement of circulating IgG and IgE food-immune complexes. J Allergy Clin Immunol 1988; 81:758-60. [PMID: 3356853 DOI: 10.1016/0091-6749(88)91050-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- A L Sheffer
- Hospital for Sick Children, Toronto, Ontario, Canada
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Husby S, Foged N, Høst A, Svehag SE. Passage of dietary antigens into the blood of children with coeliac disease. Quantification and size distribution of absorbed antigens. Gut 1987; 28:1062-72. [PMID: 3678964 PMCID: PMC1433239 DOI: 10.1136/gut.28.9.1062] [Citation(s) in RCA: 59] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The uptake of ovalbumin (OA) from egg and beta-lactoglobulin (BLG) from cow's milk into the blood was investigated for seven hours after a test meal in five children with coeliac disease on a gluten free diet and after gluten challenge, and in five children with normal jejunal mucosa. Ovalbumin was detectable by ELISA in three of five coeliac children (maximal concentrations 8-178 ng/ml serum) and in five of five controls (maximal 4-91 ng/ml serum). Beta-lactoglobulin was detected in three of five coeliac children (maximal 0.6-6 ng/ml serum) and in two of five controls (maximal 0.5 and 50 ng/ml serum). No clear relationship was seen between maximal antigen concentrations and titres of serum IgG or IgA antibodies determined by ELISA, or as percentage antigen binding in a Farr type radioimmunoassay. Ovalbumin and beta-lactoglobulin was seen in serum of all coeliac patients and controls by HPLC fractionation in combination with ELISA, either in high MW fractions, or at the Mr of native OA and BLG, respectively. In one control degradation products (about 17 kD) of BLG were detectable in serum. The serum concentrations of OA and BLG were increased on gluten challenge in four or five coeliac children, indicating increased macromolecular passage through the gut mucosa in untreated coeliac disease.
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Affiliation(s)
- S Husby
- Institute of Medical Microbiology, Odense University, Denmark
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Husby S, Svehag SE, Jensenius JC. Passage of dietary antigens in man: kinetics of appearance in serum and characterization of free and antibody-bound antigen. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 1987; 216A:801-12. [PMID: 3687554 DOI: 10.1007/978-1-4684-5344-7_93] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- S Husby
- Institute of Medical Microbiology, Odense University, Denmark
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