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Scandinavian Journal of Immunology Jan 2017Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients... (Review)
Review
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.
Topics: Animals; Antibiotic Prophylaxis; B-Lymphocytes; Cell Differentiation; Ethnicity; Humans; IgA Deficiency; Immunity; Incidence; Mutation; Phenotype; Prevalence
PubMed: 27763681
DOI: 10.1111/sji.12499 -
Journal of Gastrointestinal and Liver... Dec 2023Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto,... (Review)
Review
Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto, a strict gluten-free diet is the only effective treatment and is necessary for good control of the disease. Serological tests in current use have very high specificity and sensitivity for diagnostics, but in follow-up they have some limitations. Their levels do not accurately reflect mucosal healing, and they are unable to detect minimal transgressions in the diet. This problem is significant in patients with IgA deficiency, and there exist no robust follow-up tools for monitoring these patients' adherence to treatment. For their follow-up, we currently use IgG-based tests, and these antibodies persist for a long time even when a patient has stopped consuming gluten. More accurate and specific biomarkers are definitely needed. Adherence to a gluten-free diet is essential not only for intestinal mucosa healing and alleviation of symptoms but also for preventing complications associated with celiac disease. Here, we summarize current evidence regarding noninvasive biomarkers potentially useful for follow-up not only of patients with IgA deficiency but for all patients with celiac disease. We describe several very promising biomarkers with potential to be part of clinical practice in the near future.
Topics: Humans; Celiac Disease; Follow-Up Studies; IgA Deficiency; Glutens; Diet, Gluten-Free; Biomarkers; Immunoglobulin A
PubMed: 38147608
DOI: 10.15403/jgld-4926 -
Archivum Immunologiae Et Therapiae... Feb 2017Anaphylactic reactions are a known complication in some IgA-deficient patients receiving blood or plasma transfusions. It is of particular interest that anaphylaxis has... (Review)
Review
Anaphylactic reactions are a known complication in some IgA-deficient patients receiving blood or plasma transfusions. It is of particular interest that anaphylaxis has been observed in patients with common variable immunodeficiency (CVID) who are receiving intravenous gammaglobulin (IVIG), and in that, although these patients have an impaired response to common vaccines, they retain the ability to produce autoantibodies. In this study, we review IgA antibodies (both IgG- and IgE-mediated reactions) in patients with CVID and hypogammaglobulinemia, anaphylaxis in antibody immunodeficient patients receiving IVIG, and proposed mechanisms of desensitization and prevention of anaphylactic reactions in immunodeficient patients receiving IVIG. We summarize and assess the 23 case reports documented in the literature that have described anaphylactic reactions in immunodeficient patients receiving IVIG since 1962 until currently, and make a comparison of their immunoglobulin levels, IgG anti-IgA, IgE anti-IgA, concentration of IVIG, IgA content in IVIG, method used to detect antibodies, length of treatment, and any subsequent tolerated treatment documented.
Topics: Agammaglobulinemia; Anaphylaxis; Antibodies, Anti-Idiotypic; Autoantibodies; Female; Humans; IgA Deficiency; Immunoglobulin E; Immunoglobulin G; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Male; Treatment Outcome
PubMed: 27412077
DOI: 10.1007/s00005-016-0410-1 -
Frontiers in Immunology 2021Selective IgA deficiency (SIgAD), characterized by a serum IgA level below 0.07 mg/ml, while displaying normal serum levels of IgM and IgG antibodies, is the most... (Review)
Review
Selective IgA deficiency (SIgAD), characterized by a serum IgA level below 0.07 mg/ml, while displaying normal serum levels of IgM and IgG antibodies, is the most frequently occurring primary immunodeficiency that reveals itself after the first four years after birth. These individuals with SIgAD are for the majority healthy and even when they are identified they are usually not investigated further or followed up. However, recent studies show that newborns and young infants already display clinical manifestations of this condition due to aberrancies in their immune defense. Interestingly, there is a huge heterogeneity in the clinical symptoms of the affected individuals. More than 50% of the affected individuals do not have clinical symptoms, while the individuals that do show clinical symptoms can suffer from mild to severe infections, allergies and autoimmune diseases. However, the reason for this heterogeneity in the manifestation of clinical symptoms of the individuals with SIgAD is unknown. Therefore, this review focusses on the characteristics of innate immune system driving T-cell independent IgA production and providing a mechanism underlying the development of SIgAD. Thereby, we focus on some important genes, including TNFRSF13B (encoding TACI), associated with SIgAD and the involvement of epigenetics, which will cover the methylation degree of TNFRSF13B, and environmental factors, including the gut microbiota, in the development of SIgAD. Currently, no specific treatment for SIgAD exists and novel therapeutic strategies could be developed based on the discussed information.
Topics: Epigenesis, Genetic; Gastrointestinal Microbiome; Humans; IgA Deficiency; Immunity, Innate; Immunoglobulin A; Infant; Infant, Newborn; T-Lymphocytes; Transmembrane Activator and CAML Interactor Protein
PubMed: 33981304
DOI: 10.3389/fimmu.2021.649112 -
The Journal of Allergy and Clinical... Sep 2023Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is...
BACKGROUND
Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown.
OBJECTIVES
Our goal was to study the impact of IgA on gut mycobiota ecology.
METHODS
The Fungi-Flow method was used to characterize fecal, systemic, and maternal IgA, IgM, and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HDs) (n = 34, 31, and 20, respectively) and to also compare gut mycobiota opsonization by secretory antibodies in HDs (n = 28) and patients with selective IgA deficiency (SIgAd) (n = 12). Stool mycobiota composition was determined by internal transcribed spacer gene sequencing in HDs (n = 23) and patients with SIgAd (n = 17). Circulating CD4 T-cell cytokine secretion profiles were determined by intracellular staining. The impact of secretory IgA, purified from breast milk (n = 9), on Candidaalbicans growth and intestinal Caco-2 cell invasion was tested in vitro.
RESULTS
Homeostatic IgA binds commensal fungi with a body fluid-selective pattern of recognition. In patients with SIgAd, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut Calbicans overgrowth nevertheless occurs in this condition but only in clinically symptomatic patients with decreased T17/T22 T-cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by Calbicans and therefore exert control on this pathobiont.
CONCLUSION
IgA has a selective impact on Calbicans ecology to preserve fungal-host mutualism.
Topics: Female; Humans; Candida albicans; Caco-2 Cells; IgA Deficiency; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin M
PubMed: 37169153
DOI: 10.1016/j.jaci.2023.03.033 -
Clinical Immunology (Orlando, Fla.) May 2017Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and...
Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.
Topics: Adolescent; Adult; Agammaglobulinemia; Ataxia Telangiectasia; Ataxia Telangiectasia Mutated Proteins; Cause of Death; Child; Cohort Studies; Female; Humans; Hyper-IgM Immunodeficiency Syndrome; IgA Deficiency; Immunoglobulin G; Immunologic Deficiency Syndromes; Life Expectancy; Male; Middle Aged; Mutation; Neoplasms; Odds Ratio; Phenotype; Proportional Hazards Models; Retrospective Studies; Survival Rate; Young Adult
PubMed: 28126470
DOI: 10.1016/j.clim.2017.01.009 -
Frontiers in Cellular and Infection... 2021A large repertoire of IgA is produced by B lymphocytes with T-independent and T-dependent mechanisms useful in defense against pathogenic microorganisms and to reduce... (Review)
Review
A large repertoire of IgA is produced by B lymphocytes with T-independent and T-dependent mechanisms useful in defense against pathogenic microorganisms and to reduce immune activation. IgA is active against several pathogens, including rotavirus, poliovirus, influenza virus, and SARS-CoV-2. It protects the epithelial barriers from pathogens and modulates excessive immune responses in inflammatory diseases. An early SARS-CoV-2 specific humoral response is dominated by IgA antibodies responses greatly contributing to virus neutralization. The lack of anti-SARS-Cov-2 IgA and secretory IgA (sIgA) might represent a possible cause of COVID-19 severity, vaccine failure, and possible cause of prolonged viral shedding in patients with Primary Antibody Deficiencies, including patients with Selective IgA Deficiency. Differently from other primary antibody deficiency entities, Selective IgA Deficiency occurs in the vast majority of patients as an asymptomatic condition, and it is often an unrecognized, Studies are needed to clarify the open questions raised by possible consequences of a lack of an IgA response to SARS-CoV-2.
Topics: Antibodies, Neutralizing; Antibodies, Viral; COVID-19; Humans; IgA Deficiency; Immunoglobulin A; SARS-CoV-2; Virus Shedding
PubMed: 33889552
DOI: 10.3389/fcimb.2021.655896 -
International Archives of Allergy and... 2019Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in... (Review)
Review
Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.
Topics: Animals; Apoptosis; Cytokines; Disease Models, Animal; Genetic Predisposition to Disease; Humans; IgA Deficiency; Microbiota; Receptors, Immunologic
PubMed: 31091523
DOI: 10.1159/000499044 -
Frontiers in Immunology 2018Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological... (Review)
Review
Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological phenotypes can result in dysregulation of the immune system humoral compartment, including class-switch recombination (CSR) defects associated with hyper-IgM (HIGM) syndromes. The CSR/HIGM syndromes are defined by the presence of normal or elevated plasma IgM levels in the context of low levels of switched IgG, IgA, and IgE isotypes. Recently described autosomal dominant gain-of-function (GOF) mutations in and cause combined immunodeficiencies that can also present as CSR/HIGM defects. These defects, their pathophysiology and derived clinical manifestations are described in depth. Previously reported forms of CSR/HIGM syndromes are briefly reviewed and compared to the phosphoinositide 3-kinase (PI3K) pathway defects. Diseases involving the PI3K pathway represent a distinctive subset of CSR/HIGM syndromes, presenting with their own characteristic clinical and laboratory attributes as well as individual therapeutic approaches.
Topics: Class I Phosphatidylinositol 3-Kinases; Class Ia Phosphatidylinositol 3-Kinase; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunity, Humoral; Immunoglobulin Class Switching; Immunoglobulin Isotypes; Mutation; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 30319630
DOI: 10.3389/fimmu.2018.02172