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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 -
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 -
American Family Physician Nov 2003Primary immunodeficiencies include a variety of disorders that render patients more susceptible to infections. If left untreated, these infections may be fatal. The... (Review)
Review
Primary immunodeficiencies include a variety of disorders that render patients more susceptible to infections. If left untreated, these infections may be fatal. The disorders constitute a spectrum of more than 80 innate defects in the body's immune system. Primary immunodeficiencies generally are considered to be relatively uncommon. There may be as many as 500,000 cases in the United States, of which about 50,000 cases are diagnosed each year. Common primary immunodeficiencies include disorders of humoral immunity (affecting B-cell differentiation or antibody production), T-cell defects and combined B- and T-cell defects, phagocytic disorders, and complement deficiencies. Major indications of these disorders include multiple infections despite aggressive treatment, infections with unusual or opportunistic organisms, failure to thrive or poor growth, and a positive family history. Early recognition and diagnosis can alter the course of primary immunodeficiencies significantly and have a positive effect on patient outcome.
Topics: Anti-Bacterial Agents; Bone Marrow Transplantation; Contraindications; Humans; IgA Deficiency; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Transfusion Reaction; Vaccines
PubMed: 14655810
DOI: No ID Found -
Journal of Clinical Immunology Jan 2010Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other... (Review)
Review
INTRODUCTION
Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. IGA AND ITS FUNCTIONS: Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals.
PATHOGENESIS
In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency.
CONCLUSION
The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency.
Topics: Animals; Antibiotic Prophylaxis; Autoimmunity; Bacterial Infections; Gastrointestinal Tract; Humans; IgA Deficiency; Immunity, Mucosal; Immunoglobulin A; Inflammatory Bowel Diseases; Mice; Respiratory Tract Diseases
PubMed: 20101521
DOI: 10.1007/s10875-009-9357-x -
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 -
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 -
Medicina (Kaunas, Lithuania) Jul 2019Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD... (Review)
Review
Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.
Topics: Anemia; Celiac Disease; Hematologic Diseases; Humans; IgA Deficiency; Lymphoma
PubMed: 31311098
DOI: 10.3390/medicina55070373 -
Molecular Medicine (Cambridge, Mass.) 2011Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety... (Review)
Review
Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.
Topics: Autoimmune Diseases; Biomarkers; Humans; IgA Deficiency
PubMed: 21826374
DOI: 10.2119/molmed.2011.00195 -
Innate Immunity Jan 2018The critical role of the CD40/CD40L pathway in B-cell proliferation, immunoglobulin (Ig) isotype switching and germinal center formation has been studied and described... (Review)
Review
The critical role of the CD40/CD40L pathway in B-cell proliferation, immunoglobulin (Ig) isotype switching and germinal center formation has been studied and described extensively in previous literature. Interruption of the CD40/CD40L signal causes hyper-IgM (HIGM) syndrome, which has been classified and recognized as a group of rare inherited immune deficiency disorders. Defects in CD40 and CD40L interactions or in downstream signaling molecules, including activation-induced cytidine deaminase, uracyl-DNA-glycosylase, NF-κB and DNA repair enzymes, result in an increased level of serum IgM and a significantly decreased or absent level of IgA, IgG and IgE that is accompanied by severe recurrent infections and autoimmune diseases. Many genetic defects in HIGM have been identified and, as a result, it is possible for patients to be definitively diagnosed by gene sequencing and to delineate the immunological features of the patients. Modifying the CD40/CD40L signaling pathway may offer the possibility of restoring the normal serum Ab production and curing the immunodeficiency. Hematopoietic stem cell transplantation has achieved a high rate of success using a sibling donor. In addition, successful examples of treating other immunodeficiencies using gene therapy indicated that there was a possibility of eradicating HIGM with this approach. In this review, we summarize the current drugs and a variety of therapeutic approaches for the treatment of the HIGM syndrome by interfering with the defective CD40/CD40L pathway.
Topics: CD40 Antigens; CD40 Ligand; Humans; Hyper-IgM Immunodeficiency Syndrome; Signal Transduction
PubMed: 29132233
DOI: 10.1177/1753425917739681