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Medicina (Kaunas, Lithuania) Jan 2022Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA... (Review)
Review
Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.
Topics: Autoimmunity; B-Lymphocytes; Humans; Hypersensitivity; IgA Deficiency; Prevalence
PubMed: 35056437
DOI: 10.3390/medicina58010129 -
Expert Review of Clinical Immunology Apr 2017The most common humoral immunodeficiency is IgA deficiency. One of the first papers addressing the cellular and molecular mechanisms underlying IgA deficiency indicated... (Review)
Review
The most common humoral immunodeficiency is IgA deficiency. One of the first papers addressing the cellular and molecular mechanisms underlying IgA deficiency indicated that immature IgA-positive B-lymphocytes are present in these patients. This suggests that the genetic background for IgA is still intact and that class switching can take place. At this moment, it cannot be ruled out that genetic as well as environmental factors are involved. Areas covered: A clinical presentation, the biological functions of IgA, and the management of IgA deficiency are reviewed. In some IgA deficient patients, a relationship with a loss-of-function mutation in the TACI (transmembrane activator and calcium-modulating cyclophilin ligand interaction) gene has been found. Many other genes also have been associated. Gut microbiota are an important environmental trigger for IgA synthesis. Expert commentary: Expression of IgA deficiency is due to both genetic and environmental factors and a role for gut microbiota cannot be excluded.
Topics: Animals; B-Cell Activating Factor; B-Lymphocytes; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; IgA Deficiency; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin Class Switching; Microbiota; Polymorphism, Genetic; Precursor Cells, B-Lymphoid; Transmembrane Activator and CAML Interactor Protein; Tumor Necrosis Factor Ligand Superfamily Member 13
PubMed: 27776452
DOI: 10.1080/1744666X.2017.1248410 -
Journal of Clinical Immunology Nov 2014In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma,... (Review)
Review
In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.
Topics: Age of Onset; Animals; B-Lymphocytes; Disease Models, Animal; Humans; Interleukin-2; Lymphoproliferative Disorders; Protein-Tyrosine Kinases; T-Lymphocytes
PubMed: 25339095
DOI: 10.1007/s10875-014-0110-8 -
International Journal of Molecular... Jul 2020In recent years, the incidence of immune-mediated gastrointestinal disorders, including celiac disease (CeD) and inflammatory bowel disease (IBD), is increasingly... (Review)
Review
In recent years, the incidence of immune-mediated gastrointestinal disorders, including celiac disease (CeD) and inflammatory bowel disease (IBD), is increasingly growing worldwide. This generates a need to elucidate the conditions that may compromise the diagnosis and treatment of such gastrointestinal disorders. It is well established that primary immunodeficiencies (PIDs) exhibit gastrointestinal manifestations and mimic other diseases, including CeD and IBD. PIDs are often considered pediatric ailments, whereas between 25 and 45% of PIDs are diagnosed in adults. The most common PIDs in adults are the selective immunoglobulin A deficiency (SIgAD) and the common variable immunodeficiency (CVID). A trend to autoimmunity occurs, while gastrointestinal disorders are common in both diseases. Besides, the occurrence of CeD and IBD in SIgAD/CVID patients is significantly higher than in the general population. However, some differences concerning diagnostics and management between enteropathy/colitis in PIDs, as compared to idiopathic forms of CeD/IBD, have been described. There is an ongoing discussion whether CeD and IBD in CVID patients should be considered a true CeD and IBD or just CeD-like and IBD-like diseases. This review addresses the current state of the art of the most common primary immunodeficiencies in adults and co-occurring CeD and IBD.
Topics: Adult; Celiac Disease; Child; Common Variable Immunodeficiency; Diagnosis, Differential; Gastrointestinal Tract; Humans; IgA Deficiency; Inflammatory Bowel Diseases
PubMed: 32718006
DOI: 10.3390/ijms21155223 -
Iranian Journal of Immunology : IJI May 2023Individuals with Selective Immunoglobulin-A Deficiency (SIgAD) are often asymptomatic, and symptomatic SIgAD patients often have autoimmune comorbidities. A 48-year-old... (Review)
Review
Individuals with Selective Immunoglobulin-A Deficiency (SIgAD) are often asymptomatic, and symptomatic SIgAD patients often have autoimmune comorbidities. A 48-year-old Han Chinese man presented with abdominal discomfort, hematochezia, and a large tumor in the anogenital region. The primary diagnosis of SIgAD was based on the patient's age, serum IgA concentration (0.067 g/L), and the evidence of chronic respiratory infection. No other immunoglobulin deficiency or evidence of immunosuppression was present. The primary diagnosis of giant condyloma acuminatum was based on human papilloma virus-6-positive laboratory results and histological characteristics. The tumor and adjacent skin lesions were resected. Hemoglobin concentration fell to 5.50 g/dL, and an emergency erythrocyte transfusion was performed. The body temperature increased to 39.8 ºC, suggesting a transfusion reaction, and 5 mg dexamethasone was administered intravenously. Hemoglobin concentration stabilized at 10.5 g/dL. The clinical signs and laboratory results indicated autoimmune hemolytic anemia, systemic lupus erythematosus, and Hashimoto's thyroiditis. Abdominal discomfort and hematochezia subsided. Though uncommon, the manifestation of multiple autoimmune comorbidities can occur in SIgAD patients. Further research is needed regarding the causes of SIgAD and the autoimmune disorders that often occur as comorbidities.
Topics: Male; Humans; Middle Aged; IgA Deficiency; Autoimmune Diseases; Immunoglobulins; Hemoglobins
PubMed: 37158141
DOI: 10.22034/iji.2023.97452.2513 -
Clinical Reviews in Allergy & Immunology Feb 2020Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L). Although the... (Review)
Review
Selective immunoglobulin A deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L). Although the majority of people born with IgA deficiency lead normal lives without significant pathology, there is nonetheless a significant association of IgA deficiency with mucosal infection, increased risks of atopic disease, and a higher prevalence of autoimmune disease. To explain these phenomena, we have performed an extensive literature review to define the geoepidemiology of IgA deficiency and particularly the relative risks for developing systemic lupus erythematosus, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and vitiligo; these diseases have strong data to support an association. We also note weaker associations with scleroderma, celiac disease, autoimmune hepatitis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia. Minimal if any associations are noted with myasthenia gravis, lichen planus, and multiple sclerosis. Finally, more recent data provide clues on the possible immunologic mechanisms that lead to the association of IgA deficiency and autoimmunity; these lessons are important for understanding the etiology of autoimmune disease.
Topics: Autoimmune Diseases; Autoimmunity; Comorbidity; Disease Susceptibility; Humans; IgA Deficiency; Immunoglobulin A; Phenotype; Quality of Life; Symptom Assessment
PubMed: 31267472
DOI: 10.1007/s12016-019-08756-7 -
Critical Reviews in Immunology 2021Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other...
Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other behavioral disorders, among other examples, are now recognized to be associated with the complex constitution of the body's microbiome. Recent findings demonstrate that the microbial composition, i.e., pathogenic, symbionts, and commensal viruses, bacteria, or yeast mainly in the gut, is strongly associated with susceptibility/resistance to several classes of diseases or its therapeutic response. This Special Issue focuses on the processes that link the human microbiome to three classes of diseases; immunodeficiency, autoimmunity, and cancer. Review articles cover aspects of the recent progress in selective immunoglobulin A (IgA) deficiency, Sjörgren's syndrome, breast cancer.
Topics: Autoimmunity; Gastrointestinal Microbiome; Humans; IgA Deficiency; Immune System; Microbiota
PubMed: 35695642
DOI: 10.1615/CritRevImmunol.2022043499 -
Pediatric Allergy and Immunology :... Sep 2017The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey . Since then, a lot of new information on the role of subclasses and their... (Review)
Review
The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey . Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children.
Topics: Child; Humans; IgG Deficiency; Immunoglobulin G; Immunologic Factors
PubMed: 28686792
DOI: 10.1111/pai.12757 -
Immunologic Research Feb 2024Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and is significantly associated with Celiac Disease (CD), which recognizes a specific...
Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and is significantly associated with Celiac Disease (CD), which recognizes a specific background of human leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A number of studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles are included in the main haplotypes linked to this primary immunodeficiency. In this preliminary study, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgA levels: 108 serum samples from the bone marrow donors' registry were analyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although total serum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donors were not different, we observed a statistically significant difference (p=0.0118) in total serum IgA levels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared to HLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelic variant in the determination of total serum IgA levels, at least in patients affected with IgA deficiency and/or otherwise predisposed to it; however, larger and more standardized studies are needed to confirm this speculation.
Topics: Humans; HLA-DQ beta-Chains; Genotype; Haplotypes; IgA Deficiency; Immunoglobulin A; Alleles; Gene Frequency; Genetic Predisposition to Disease
PubMed: 37725324
DOI: 10.1007/s12026-023-09420-1 -
Scientific Reports Jul 2021Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from...
Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens. Recently, IgA has been shown to be involved in gut homeostatic regulation by 'recognizing' and shaping our commensal microbes. Paradoxically, yet selective IgA-deficiency is often described as asymptomatic and there is a paucity of studies only focused on the mice and human gut microbiome context fully ignoring other niches of our body and our commensal viruses. Here, we used as a model the human oral cavity and employed a holistic view and studied the impact of IgA deficiency and also common variable IgA and IgM immunodeficiencies (CVID), on both the human virome and microbiome. Unexpectedly, metagenomic and experimental data in human IgA deficiency and CVID indicate minimal-moderate changes in microbiome and virome composition compared to healthy control group and point out to a rather functional, resilient oral commensal viruses and microbes. However, a significant depletion (two fold) of bacterial cells (p-value < 0.01) and viruses was observed in IgA-deficiency. Our results demonstrate that, within the limits of our cohort, IgA role is not critical for maintaining a rather functional salivary microbiome and suggest that IgA is not a major influence on the composition of abundant commensal microbes.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; IgA Deficiency; Immunoglobulin A; Immunoglobulin M; Male; Metagenomics; Microbiota; Middle Aged; Mouth; Saliva; Virome; Young Adult
PubMed: 34290346
DOI: 10.1038/s41598-021-94507-8