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Dubois C, Ducas É, Laforce-Lavoie A, Robidoux J, Delorme A, Live LS, Brouard D, Masson JF. A portable surface plasmon resonance (SPR) sensor for the detection of immunoglobulin A in plasma. Transfusion 2024; 64:881-892. [PMID: 38591151 DOI: 10.1111/trf.17818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 03/05/2024] [Accepted: 03/20/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND A life-threatening anaphylactic shock can occur if a patient with undiagnosed immunoglobulin A (IgA) deficiency (i.e., IgA levels <500 ng/mL) receives IgA-containing blood, hence the need for a rapid, point-of-care (POC) method for IgA deficiency screening. Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect IgA, but this method requires trained specialists and ≥24 h to obtain a result. We developed a surface plasmon resonance (SPR)-based protocol to identify IgA-deficient patients or donors within 1 h. MATERIALS AND METHODS The SPR sensor relies on the detection of IgAs captured by primary antibodies adsorbed on the SPR chip and quantified with secondary antibodies. The sensor was calibrated from 0 to 2000 ng/mL in buffer, IgA-depleted human serum, and plasma samples from IgA-deficient individuals. A critical concentration of 500 ng/mL was set for IgA deficiency. The optimized sensor was then tested on eight plasma samples with known IgA status (determined by ELISA), including five with IgA deficiency and three with normal IgA levels. RESULTS The limit of detection was estimated at 30 ng/mL in buffer and 400 ng/mL in diluted plasma. The results obtained fully agreed with ELISA among the eight plasma samples tested. The protocol distinguished IgA-deficient from normal samples, even for samples with an IgA concentration closer to critical concentration. DISCUSSION In conclusion, we developed a reliable POC assay for the quantification of IgA in plasma. This test may permit POC testing at blood drives and centralized centers to maintain reserves of IgA-deficient blood and in-hospital testing of blood recipients.
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Affiliation(s)
- Caroline Dubois
- Département de Chimie, Quebec Center for Advanced Materials, Regroupement Québécois sur les Matériaux de Pointe, and Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Institut Courtois, Université de Montréal, Montréal, Canada
| | - Éric Ducas
- Héma-Québec, Affaires Médicales et Innovation, Québec City, Québec, Canada
| | | | - Jonathan Robidoux
- Héma-Québec, Affaires Médicales et Innovation, Québec City, Québec, Canada
| | - Alexandre Delorme
- Département de Chimie, Quebec Center for Advanced Materials, Regroupement Québécois sur les Matériaux de Pointe, and Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Institut Courtois, Université de Montréal, Montréal, Canada
| | | | - Danny Brouard
- Héma-Québec, Affaires Médicales et Innovation, Québec City, Québec, Canada
| | - Jean-François Masson
- Département de Chimie, Quebec Center for Advanced Materials, Regroupement Québécois sur les Matériaux de Pointe, and Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Institut Courtois, Université de Montréal, Montréal, Canada
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Stubbs J, Klompas A, Thalji L. Transfusion Therapy in Specific Clinical Situations. Transfus Med 2021. [DOI: 10.1002/9781119599586.ch11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Study of selective immunoglobulin A deficiency among Egyptian patients with food allergy. Cent Eur J Immunol 2021; 45:184-188. [PMID: 33456329 PMCID: PMC7792446 DOI: 10.5114/ceji.2020.97907] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 02/12/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction IgA deficiency is one of the commonest primary antibody deficiencies. Although many affected individuals could be asymptomatic, selected patients suffer from recurrent mucosal infections, allergies, and autoimmune diseases. Aim of the study To investigate the prevalence of IgA deficiency among Egyptian patients with food allergy. Material and methods We studied 100 patients (62 males, 38 females; mean age, 28.6 years) with multiple food allergies who were recruited on the basis of adequate immunological assessment by history, skin prick test, and confirmed by open challenge test as well as 50 healthy controls. Measurement of levels of IgE and IgA using ELISA technique were performed for all patients and controls. Results Deficiency of IgA was detected in 67% of patients with food allergy. Serum IgA levels were significantly lower among patients with food allergy (67.3 µg/ml; range, 56.7-72.0 µg/ml) as compared to healthy control (78.6 µg/ml; range, 72.8-84 µg/ml). Both IgA and IgE levels were not statistically different between patients with food allergy only and those with combined food and aeroallergen. Among food allergic group, serum IgA levels were inversely correlated with serum IgE levels (r = –0.314, p < 0.001). Conclusions Manifestations of atopy, such as food allergy might be a present feature before diagnosis of primary immune deficiency diseases as IgA deficiency.
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4
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Cardigan R, New HV, Tinegate H, Thomas S. Washed red cells: theory and practice. Vox Sang 2020; 115:606-616. [DOI: 10.1111/vox.12971] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 05/27/2020] [Accepted: 06/09/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Rebecca Cardigan
- Department of Haematology NHS Blood & Transplant University of Cambridge Cambridge UK
| | - Helen V. New
- Department of Haematology NHS Blood & Transplant Imperial College London London UK
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Cereser L, De Carli M, d’Angelo P, Zanelli E, Zuiani C, Girometti R. High-resolution computed tomography findings in humoral primary immunodeficiencies and correlation with pulmonary function tests. World J Radiol 2018; 10:172-183. [PMID: 30568751 PMCID: PMC6288673 DOI: 10.4329/wjr.v10.i11.172] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 09/22/2018] [Accepted: 10/07/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To compare high-resolution computed tomography (HRCT) findings between humoral primary immunodeficiencies (hPIDs) subtypes; to correlate these findings to pulmonary function tests (PFTs).
METHODS We retrospectively identified 52 consecutive adult patients with hPIDs who underwent 64-row HRCT and PFTs at the time of diagnosis. On a per-patient basis, an experienced radiologist recorded airway abnormalities (bronchiectasis, airway wall thickening, mucus plugging, tree-in-bud, and air-trapping) and parenchymal-interstitial abnormalities (consolidations, ground-glass opacities, linear and/or irregular opacities, nodules, and bullae/cysts) found on HRCT. The chi-square test was performed to compare the prevalence of each abnormality among patients with different subtypes of hPIDs. Overall logistic regression analysis was performed to assess whether HRCT findings predicted obstructive and/or restrictive PFTs results (absent-to-mild vs moderate-to-severe).
RESULTS Thirty-eight of the 52 patients with hPIDs showed common variable immunodeficiency disorders (CVID), while the remaining 14 had CVID-like conditions (i.e., 11 had isolated IgG subclass deficiencies and 3 had selective IgA deficiencies). The prevalence of most HRCT abnormalities was not significantly different between CVID and CVID-like patients (P > 0.05), except for linear and/or irregular opacities (prevalence of 31.6% in the CVID group and 0 in the CVID-like group; P = 0.0427). Airway wall thickening was the most frequent HRCT abnormality found in both CVID and CVID-like patients (71% of cases in both groups). The presence of tree-in-bud abnormalities was an independent predictor of moderate-to-severe obstructive defects at PFTs (Odds Ratio, OR, of 18.75, P < 0.05), while the presence of linear and/or irregular opacities was an independent predictor of restrictive defects at PFTs (OR = 13.00; P < 0.05).
CONCLUSION CVID and CVID-like patients showed similar HRCT findings. Tree-in-bud and linear and/or irregular opacities predicted higher risks of, respectively, obstructive and restrictive defects at PFTs.
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Affiliation(s)
- Lorenzo Cereser
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Marco De Carli
- Second Unit of Internal Medicine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Paola d’Angelo
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
- Department of Imaging, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy
| | - Elisa Zanelli
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Chiara Zuiani
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Rossano Girometti
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
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6
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Warkentin TE, Morin PA, Heddle NM. Neutropenia and monocytopenia in recurrent anaphylactoid reactions after red blood cell transfusions in a woman with immunoglobulin A (IgA) deficiency and anti-IgA. Transfusion 2018; 58:2320-2325. [PMID: 30178875 DOI: 10.1111/trf.14894] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/14/2018] [Accepted: 06/16/2018] [Indexed: 12/01/2022]
Abstract
BACKGROUND Transfusion-associated anaphylaxis has been associated with anti-immunoglobulin A (anti-IgA) of IgG class in patients with IgA deficiency. In recent years, however, the frequency and clinical impact of this syndrome has been questioned. We present a case of recurrent red blood cell (RBC) transfusion-associated anaphylactoid reactions (rigors, hypertension, transient monocytopenia, and neutropenia) associated with anti-IgA. CASE REPORT An 88-year-old woman developed anemia after a traumatic right humerus fracture. After receiving approximately 100 mL of RBCs she developed rigors and hypertension; her absolute neutrophil and monocyte counts decreased by 73 and 100%, respectively. All symptoms and signs resolved, and her blood counts normalized. A second RBC transfusion was given, with recurrence of rigors, hypertension, neutropenia, and monocytopenia (69 and 100% declines, respectively), along with fever. All tests for hemolysis were negative. She then received two transfusions of washed RBCs, without incident. The patient was found to be deficient in IgA (<0.05 mg/dL). Further, anti-IgA of IgG class antibodies were detected in high levels by enzyme-linked immunosorbent assay (>1000 U/mL). We reviewed case reports, case series, and reviews of IgA deficiency-associated reactions, examining whether hypertensive reactions and acute neutropenia and/or monocytopenia have been associated with anti-IgA reactions. RESULTS Reports of reactions associated with anti-IgA emphasize hypotension and are generally classified as "anaphylactic or anaphylaxis." No previous reports described neutropenia or monocytopenia. CONCLUSION Our case suggests that adverse transfusion reactions associated with anti-IgA of IgG class may sometimes be characterized by anaphylactoid features such as rigors and hypertension, with transient monocytopenia and neutropenia.
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Affiliation(s)
- Theodore E Warkentin
- Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,McMaster Centre for Transfusion Research, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Pierre-Aurèle Morin
- Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Nancy M Heddle
- Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,McMaster Centre for Transfusion Research, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
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Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. Selective IgA Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management. Scand J Immunol 2017; 85:3-12. [PMID: 27763681 DOI: 10.1111/sji.12499] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 10/18/2016] [Indexed: 12/30/2022]
Abstract
Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients suffer from different clinical complications such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Pathogenesis of SIgAD is still unknown; however, a defective terminal differentiation of B cells and defect in switching to IgA-producing plasma cells are presumed to be responsible. Furthermore, some cytogenic defects and monogenic mutations are associated with SIgAD. There is no specific treatment for patients with symptomatic IgA deficiency, although prophylactic antibiotic therapy along with circumstantial immunoglobulin replacement with justification and supportive care (using a product that contains minimal IgA) could be helpful for patients with a severe phenotype. The epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis, management and treatment in patients with SIgAD have been reviewed.
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Affiliation(s)
- R Yazdani
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Molecular Immunology Interest Group (MIIG), Universal Scientific Education and Research Network (USERN), Isfahan, Iran
| | - G Azizi
- Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran.,Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran
| | - H Abolhassani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - A Aghamohammadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Fouda GG, Eudailey J, Kunz EL, Amos JD, Liebl BE, Himes J, Boakye-Agyeman F, Beck K, Michaels AJ, Cohen-Wolkowiez M, Haynes BF, Reimann KA, Permar SR. Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization. Mucosal Immunol 2017; 10:228-237. [PMID: 27072605 PMCID: PMC5063654 DOI: 10.1038/mi.2016.32] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 02/22/2016] [Indexed: 02/07/2023]
Abstract
We investigated the mucosal distribution and neutralization potency of rhesus recombinant versions of the HIV-specific, broadly neutralizing antibody b12 (RhB12) following intravenous administration to lactating rhesus monkeys. IgG and dimeric IgA (dIgA) administration resulted in high plasma concentrations of broadly neutralizing antibody (bnAb), but the monomeric IgA (mIgA) was rapidly cleared from the systemic compartment. Interestingly, differences in the distribution of the RhB12 isoform were observed between the mucosal compartments. The peak concentration of RhB12 IgG was higher than dIgA in saliva, rectal, and vaginal secretions, but the bnAb concentration in milk was one to two logs higher after dIgA administration than with IgG or mIgA infusion. Neutralization was observed in plasma of all animals, but only those infused with RhB12 dIgA showed moderate levels of virus neutralization in milk. Remarkably, virus-specific secretory IgA was detected in mucosal compartments following dIgA administration. The high milk RhB12 dIgA concentration suggests that passive immunization with dIgA could be more effective than IgG to inhibit virus in breast milk.
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Affiliation(s)
- Genevieve G. Fouda
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Joshua Eudailey
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Erika L. Kunz
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Joshua D. Amos
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Brooke E. Liebl
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Jonathan Himes
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | | | - Krista Beck
- Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC
| | | | | | - Barton F. Haynes
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
| | - Keith A. Reimann
- MassBiologics, University of Massachusetts Medical School, Boston, MA
| | - Sallie R. Permar
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC
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9
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Urbonas V, Sadauskaite J, Cerkauskiene R, Kaminskas A, Mäki M, Kurppa K. Population-Based Screening for Selective Immunoglobulin A (IgA) Deficiency in Lithuanian Children Using a Rapid Antibody-Based Fingertip Test. Med Sci Monit 2016; 22:4773-4778. [PMID: 27920422 PMCID: PMC5144930 DOI: 10.12659/msm.898269] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 04/24/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Selective immunoglobulin A (IgA) deficiency is the most common inherited immunodeficiency disorder worldwide. An early diagnosis is advocated because of the increased risk of infections, autoimmune diseases, and allergic reactions. We investigated the usefulness of a rapid point-of-care test in detecting for IgA deficiency in a population with a previously unknown prevalence. MATERIAL AND METHODS Altogether, 1000 children aged 11-13 years from randomly selected Lithuanian schools were enrolled. A point-of-care test with a fingertip sample was used to screen for the presence of IgA deficiency in children whose parents gave consent. Those with suspected IgA deficiency were referred to hospital for further clinical examination and confirmation of the diagnosis. In addition, their medical histories were compared with those of 30 age- and sex-matched healthy controls. RESULTS IgA deficiency was suspected in one girl and in three boys on the basis of the rapid test, and the diagnosis was confirmed for all four cases (prevalence 0.4%, 95% confidence interval 0.16-1.02%). There was no difference in disease history or complications between IgA-deficient children and healthy controls. CONCLUSIONS The rapid antibody test is a practical and accurate method to diagnose selective IgA deficiency in children. The prevalence of IgA deficiency among Lithuanian schoolchildren is 1:250.
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Affiliation(s)
- Vaidotas Urbonas
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Children’s Hospital, Vilnius University Hospital, Vilnius, Lithuania
| | | | - Rimante Cerkauskiene
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Children’s Hospital, Vilnius University Hospital, Vilnius, Lithuania
| | | | - Markku Mäki
- Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
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10
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Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015; 136:1186-205.e1-78. [PMID: 26371839 DOI: 10.1016/j.jaci.2015.04.049] [Citation(s) in RCA: 450] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 04/18/2015] [Accepted: 04/23/2015] [Indexed: 02/07/2023]
Abstract
The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
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Verma N, Grimbacher B, Hurst JR. Lung disease in primary antibody deficiency. THE LANCET RESPIRATORY MEDICINE 2015; 3:651-60. [PMID: 26188881 DOI: 10.1016/s2213-2600(15)00202-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 05/11/2015] [Accepted: 05/11/2015] [Indexed: 12/25/2022]
Abstract
This Review summarises current knowledge on the pulmonary manifestations of primary antibody deficiency (PAD) syndromes in adults. We describe the major PAD syndromes, with a particular focus on common variable immunodeficiency (CVID). Respiratory infection is a common presenting feature of PAD syndromes. Respiratory complications are frequent and responsible for much of the morbidity and mortality associated with these syndromes. Respiratory complications include acute infections, the sequelae of infection (eg, bronchiectasis), non-infectious immune-mediated manifestations (notably the development of granulomatous-lymphocytic interstitial lung disease in CVID), and an increased risk of lymphoma. Although minor abnormalities are detectable in the lungs of most patients with CVID by CT scanning, not all patients develop lung complications. Mechanisms associated with the maintenance of lung health versus lung disease, and the development of bronchiectasis versus immune-mediated complications, are now being dissected. We review the investigation, treatment, and management strategies for PAD syndromes, and include key research questions relating to both infectious and non-infectious complications of PAD in the lung.
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Affiliation(s)
- Nisha Verma
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK
| | - Bodo Grimbacher
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK; Centre for Chronic Immunodeficiency, Medical Centre, University Hospital Freiburg, Freiburg, Germany
| | - John R Hurst
- UCL Respiratory, University College London, London, UK.
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12
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Ahmadiafshar A, Mohsenifard MR, Mazloomzadeh S. Evaluation of serum & salivary IgA in patients with type 1 diabetes. PLoS One 2015; 10:e0122757. [PMID: 25875365 PMCID: PMC4395210 DOI: 10.1371/journal.pone.0122757] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 01/27/2015] [Indexed: 01/12/2023] Open
Abstract
Background Diabetes mellitus is a common immune mediated disorder. The aim of the present study is to evaluate the level of serum and salivary IgA levels in patients with Type 1 diabetes. Material and Method In this case control study, serum and salivary IgA levels of patients with diabetes type 1 and similar non diabetes subjects were measured. Age, gender, duration of diabetes and the last HbA1c level of diabetic patients were also studied. Data was analyzed by SPSS software. Results Two hundred and fifty subjects (126 diabetics and 124 non diabetics) were enrolled in the study. The mean value of serum IgA in patients with Type 1 Diabetes and controls was 1.77± 1.55 g/lit and 2.39± 1.52 g/lit, respectively. The mean salivary IgA level in diabetics and controls was 276 ± 162.5 40 μg/ml and 129 ± 112.2 40 μg/ml, respectively. Selective IgA deficiency was detected in two (1.6%) and three(2.4%)cases of diabetic and control group; respectively (p=0.68). We found low salivary IgA level in 44.4% diabetic and 33.9% control (p=0.08). There was no significant correlation between serum and salivary IgA level. There was also significant association between serum IgA levels with age. Salivary IgA was significantly correlated with HbA1c level. But considering gender, duration of diabetes we didn’t find any association. Conclusion We didn't find any significant difference in serum and salivary IgA level among diabetic and non diabetics and also, no association between serum and salivary IgA levels.
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Affiliation(s)
- Akefeh Ahmadiafshar
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
- * E-mail:
| | - Mahmood Reza Mohsenifard
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Saeideh Mazloomzadeh
- Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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Späth PJ, Granata G, La Marra F, Kuijpers TW, Quinti I. On the dark side of therapies with immunoglobulin concentrates: the adverse events. Front Immunol 2015; 6:11. [PMID: 25699039 PMCID: PMC4318428 DOI: 10.3389/fimmu.2015.00011] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 01/07/2015] [Indexed: 12/26/2022] Open
Abstract
Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.
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Affiliation(s)
- Peter J. Späth
- Institute of Pharmacology, University of Berne, Berne, Switzerland
| | - Guido Granata
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Fabiola La Marra
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Taco W. Kuijpers
- Department of Pediatric Hematology, Immunology and Infectious Disease, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
| | - Isabella Quinti
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
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14
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The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes. Genes Immun 2015; 16:199-205. [PMID: 25569265 DOI: 10.1038/gene.2014.78] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/30/2014] [Accepted: 10/31/2014] [Indexed: 12/21/2022]
Abstract
Serum immunoglobulin A (IgA) concentrations were determined in 12 600 adult Swedish twins, applying a high-throughput reverse-phase protein microarray technique. The prevalence of IgA deficiency (IgAD) was found to be 1:241 in monozygotic (MZ) twins and 1:198 in dizygotic (DZ) twins. Hence, the prevalence in twins is markedly elevated as compared with the normal Swedish adult population (1:600). The twins did not show a difference in the frequency of HLA haplotypes in comparison with almost 40 000 healthy Swedish controls. As expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were overrepresented among the IgAD twins and were also associated with significantly lower mean serum IgA concentrations in the twin cohort. In contrast, significantly higher mean IgA concentrations were found among individuals carrying the protective HLA alleles B*07 and DRB1*15. Exome sequencing data from two MZ twin pairs discordant for the deficiency showed no differences between the siblings. Model fitting analyses derived a heritability of 35% and indicate that genetic influences are modestly important for IgAD. The probandwise concordance rates for IgAD were found to be 31% for MZ and 13% for DZ twins.
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Alkhairy O, Hammarström L. IgA Deficiency and Other Immunodeficiencies Causing Mucosal Immunity Dysfunction. Mucosal Immunol 2015. [DOI: 10.1016/b978-0-12-415847-4.00073-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Salama A, Kardashi R, Arbach O. Long-Term Treatment and Transfusion of Normal Blood Components Following Tolerance Induction in Patients with Anti-IgA Anaphylactic Reactions. Transfus Med Hemother 2014; 41:381-7. [PMID: 25538541 PMCID: PMC4264496 DOI: 10.1159/000366240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Accepted: 05/28/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND In general, patients with significant anti-Ig-A do not tolerate intravenous (i.v.) administration of normal blood products. Here, we present our experiences in the induction of immune tolerance (IIT) and long-term treatment in a series of such patients affected in such a way. The question whether blood components from IgA-deficient donors are required will be discussed. METHODS Ten adult patients (4 females and 6 males; age ranging from 36 to 75 years) with anti-IgA were included in this study. All patients required long-term treatment with blood components. One patient had IgA deficiency and paroxysmal nocturnal hemoglobinuria (PNH), and all other patients had common variable immunodeficiency (CVID). The particle gel immunoassay was used for the detection of anti-IgA. Immune tolerance to IgA was induced by controlled subcutaneous (s.c.) and/or i.v. infusions of IgG preparations. RESULTS Prior to IIT, anti-IgA was detectable in plasma samples of all patients and significantly diminished or abolished by controlled s.c. and/or i.v. infusions of IgG. Multiple transfusions with normal blood components could be repeatedly performed with the patient suffering from PNH without any complications. As long as i.v. IgG (IVIgG) infusions were consequently administered as individually required (intervals 2-8 weeks), none of the patients developed reactions during observation (up to 10 years). However, interruption of treatment and re-exposure to IVIgG resulted in adverse reactions. CONCLUSION Patients with significant anti-IgA can be safely desensitized and tolerate long-term IgG substitutions independent of the IgA concentration of the used blood component.
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Affiliation(s)
- Abdulgabar Salama
- Transfusion Medicine, Charité University Medicine – Campus Virchow Klinikum, and ZTB, Zentrum für Transfusionsmedizin und Zelluläre Therapie, Berlin, Germany
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Sandler SG, Eder AF, Goldman M, Winters JL. The entity of immunoglobulin A-related anaphylactic transfusion reactions is not evidence based. Transfusion 2014; 55:199-204. [PMID: 25066014 DOI: 10.1111/trf.12796] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 05/16/2014] [Accepted: 05/30/2014] [Indexed: 11/28/2022]
Affiliation(s)
- S Gerald Sandler
- Department of Pathology and Laboratory Medicine, MedStar Georgetown University Hospital, Washington, DC
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Reda SM, Yousef TA, Elfeky RA, Sallam MT, Gaafar RA. Could recurrent otitis media predict primary antibody deficiencies in Egyptian children? THE EGYPTIAN JOURNAL OF OTOLARYNGOLOGY 2014. [DOI: 10.4103/1012-5574.133179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Hansen AL, Turner TR, Yi QL, Acker JP. Quality of red blood cells washed using an automated cell processor with and without irradiation. Transfusion 2013; 54:1585-94. [DOI: 10.1111/trf.12489] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 09/23/2013] [Accepted: 09/25/2013] [Indexed: 01/18/2023]
Affiliation(s)
- Adele L. Hansen
- Research and Development; Canadian Blood Services; Edmonton Alberta Canada
| | - Tracey R. Turner
- Research and Development; Canadian Blood Services; Edmonton Alberta Canada
| | - Qi-Long Yi
- Epidemiology and Surveillance; Canadian Blood Services; Ottawa Ontario Canada
| | - Jason P. Acker
- Research and Development; Canadian Blood Services; Edmonton Alberta Canada
- Department of Laboratory Medicine and Pathology; University of Alberta; Edmonton Alberta Canada
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Palmer DS, O'Toole J, Montreuil T, Scalia V, Goldman M. Evaluation of particle gel immunoassays for the detection of severe immunoglobulin A deficiency and anti-human immunoglobulin A antibodies. Transfusion 2012; 52:1792-8. [PMID: 22229448 DOI: 10.1111/j.1537-2995.2011.03513.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Immunoglobulin A (IgA)-deficient patients with anti-IgA (Ab) require transfusions using blood components with less than 0.05 mg IgA/dL as they are known to be safe for these patients. Identification of severely IgA-deficient (IgA SD) donors involved preliminary screening by the Ouchterlony double immunodiffusion assay followed by confirmatory testing at the required level of sensitivity for IgA and Ab at an external reference laboratory. Two in vitro particle gel immunoassays (ID-PaGIA IgA deficiency test and anti-IgA test) were also evaluated for their suitability in identifying IgA SD individuals and determining their Ab status. STUDY DESIGN AND METHODS Samples from 198 donors and 36 patients, subjected to confirmatory testing for IgA SD and Ab over a 2-year period, were also evaluated using the ID-PaGIA kits. RESULTS DiaMed test sensitivity and specificity for detection of IgA SD in donors was 98% whereas for Ab, test sensitivity was 91% at a specificity of 94%. In patients, sensitivity was 94% for IgA SD and 67% for Ab, both tests at a specificity of 100%. CONCLUSIONS The ID-PaGIA IgA deficiency test was a sensitive and specific tool for identifying IgA SD donors or patients. Sensitivity of the Ab test was high for donors but reduced for patients and of high specificity in both groups. Further studies with patients are needed to confirm this latter observation. Implementation of these tests would make it possible to supply appropriate products from IgA SD donors to prevent anaphylactic transfusion reactions in patients.
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Affiliation(s)
- Douglas S Palmer
- National Testing Laboratory and Donor and Transplantation Services, Head Office, Canadian Blood Services, Ottawa, Ontario, Canada.
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Nydegger UE, Fierz W, Risch L. Benefits and risks of IgA in immunoglobulin preparations. Transfus Apher Sci 2012; 46:97-102. [PMID: 22209283 DOI: 10.1016/j.transci.2011.11.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Accepted: 11/01/2011] [Indexed: 10/14/2022]
Abstract
The case of Immunoglobulin A (IgA) in transfusion medicine is unsettled: on one hand IgA is an important component of adaptive immunity and its deficiency may cause disease, on the other its presence in blood products might induce, in rare instances, allergy-like symptoms if not anaphylaxis. The practice with i.v. immunoglobulins currently changes as up to 10% concentrated preparations are given at fast rates hence even trace amounts of IgA contained in these IgG preparations can cause unexpected (side-) effects. Fortunately, the spectrum of sensitive IgA assays, along with anti-IgA screening assays now permits laboratories to narrow down IgA-dependent transfusion reactions to the real cases, in which IgA was the decisive trigger of anaphylaxis, proven or not by the presence of anti-IgA of the IgG or even IgE class. Tolerance to allogenic IgA has recently been reported. The known association of HLA with IgA deficiency (IgAD) has now been completed with an association to the nonsynonymous variant in IFHI1, allowing physicians to more precisely spot recipients at risk for an IgA-dependent transfusion reaction. Our review, along with our own experience here in Switzerland, allows us to conclude that IgA is a beneficial antibody rather than an allergen to be placed at the end of the list of non-infectious transfusion complications such as TRALI, febrile non-hemolytic reactions, purpura or volume overload.
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Affiliation(s)
- Urs E Nydegger
- Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, CH-3097 Liebefeld bei Bern, Switzerland.
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