scholarly journals Selective IgA Deficiency and Allergy: A Fresh Look to an Old Story

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 129
Author(s):  
Bianca Laura Cinicola ◽  
Federica Pulvirenti ◽  
Martina Capponi ◽  
Marta Bonetti ◽  
Giulia Brindisi ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingyan Zhang ◽  
Dèlenn van Oostrom ◽  
JianXi Li ◽  
Huub F. J. Savelkoul

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason R. Catanzaro ◽  
Juliet D. Strauss ◽  
Agata Bielecka ◽  
Anthony F. Porto ◽  
Francis M. Lobo ◽  
...  

Abstract Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Paula F. Aarestrup ◽  
Matheus F. Aarestrup ◽  
Beatriz J. V. Aarestrup ◽  
Fernando M. Aarestrup

Selective IgA deficiency is the most common type of primary immunodeficiency, but there is not yet a specific effective treatment. The most prevalent clinical manifestations are infectious diseases of the respiratory system. We report herein the case of an 11-year-old female with selective IgA deficiency and recurring episodes of respiratory infections associated with rhinitis and asthma. We evaluated the efficacy of sublingual immunotherapy combined with inactivated whole-cell bacterial extract and Der p1-specific immunotherapy. After 18 months of clinical follow-up, we observed a significant reduction in the number of episodes of respiratory infections associated with control of atopic diseases. We also observed a 3-fold increase in serum IgA levels compared to treatment initiation. This case demonstrates the potential utility of the concurrent use of sublingual immunotherapy with inactivated whole-cell bacterial extract and Der p1 for successful control of allergy and infection in partial selective IgA deficiency.


1991 ◽  
Vol 80 (8-9) ◽  
pp. 798-804 ◽  
Author(s):  
P. C. J. DE LAAT ◽  
C. M. R. WEEMAES ◽  
R. GONERA ◽  
P. J. J. VAN MUNSTER ◽  
J. A. J. M. BAKKEREN ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Che Kang Lim ◽  
Paola G. Bronson ◽  
Jezabel Varade ◽  
Timothy W. Behrens ◽  
Lennart Hammarström

Immunoglobulin A Deficiency (IgAD) is a polygenic primary immune deficiency, with a strong genetic association to the human leukocyte antigen (HLA) region. Previous genome-wide association studies (GWAS) have identified five non-HLA risk loci (IFIH1, PVT1, ATG13-AMBRA1, AHI1 and CLEC16A). In this study, we investigated the genetic interactions between different HLA susceptibility haplotypes and non-MHC genes in IgAD. To do this, we stratified IgAD subjects and healthy controls based on HLA haplotypes (N = 10,993), and then performed GWAS to identify novel genetic regions contributing to IgAD susceptibility. After replicating previously published HLA risk haplotypes, we compared individuals carrying at least one HLA risk allele (HLA-B*08:01-DRB1*03:01-DQB1*02:01 or HLA-DRB1*07:01-DQB1*02:02 or HLA-DRB1*01-DQB1*05:01) with individuals lacking an HLA risk allele. Subsequently, we stratified subjects based on the susceptibility alleles/haplotypes and performed gene-based association analysis using 572,856 SNPs and 24,125 genes. A significant genome-wide association in STXBP6 (rs4097492; p = 7.63 × 10−9) was observed in the cohort carrying at least one MHC risk allele. We also identified a significant gene-based association for B3GNT6 (PGene = 2.1 × 10–6) in patients not carrying known HLA susceptibility alleles. Our findings indicate that the etiology of IgAD differs depending on the genetic background of HLA susceptibility haplotypes.


Author(s):  
Gavin P Spickett

Introduction Classification of immunodeficiency Clinical features of immunodeficiency Investigation of immunodeficiency Laboratory investigation Major B-lymphocyte disorders Rare antibody deficiency syndromes X-linked agammaglobulinaemia (Bruton’s disease) Common variable immunodeficiency (CVID) CVID 2: complications and treatment Selective IgA deficiency IgG subclass deficiency Specific antibody deficiency with normal serum immunoglobulins...


Author(s):  
Isabella Quinti ◽  
Eva Piano Mortari ◽  
Ane Fernandez Salinas ◽  
Cinzia Milito ◽  
Rita Carsetti

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.


2018 ◽  
Author(s):  
Jason R Catanzaro ◽  
Juliet D Strauss ◽  
Agata Bielecka ◽  
Anthony F Porto ◽  
Francis M Lobo ◽  
...  

ABSTRACTImmunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) is the most common primary immunodeficiency in humans and is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and IgA or IgM coating of the gut microbiota in 15 sIgAd subjects and 15 matched controls. Although sIgAd subjects secreted a significant amount of IgM into the intestinal lumen, this was insufficient to fully compensate for the lack of secretory IgA. Indeed, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls, which was characterized by a trend towards decreased overall microbial diversity and significant shifts in the relative abundances of specific microbial taxa. While IgA targets a defined subset of the microbiota via high-level coating, compensatory IgM binds a broader subset of the microbiota in a less targeted manner. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community that promotes human health, enhances resistance to infection, and is resilient to perturbation.


2021 ◽  
Vol 19 (1) ◽  
pp. 12-23
Author(s):  
Ceyda TUNAKAN DALGIÇ ◽  
Aytül Zerrin Sin ◽  
Fatma Ömür Ardeniz

ABSTRACT Objective: Primary immunodeficiencies (PIDs) consist of genetically heterogeneous disorders. The spectrum can include infectious diseases, malignancy, allergy, and autoimmunity. We aimed to analyze the frequency and variety of autoimmune diseases (ADs) in PIDs and describe their clinical and laboratory features. Materials and Methods: Ninety-two patients with PID followed by Ege University Medical Faculty between 2000 and 2017 were enrolled in this retrospective, cross-sectional study. All patients’ medical records were reviewed using the demographic information, type of PIDs and ADs, ADs-related autoantibodies, and basic and immunologic laboratory findings. ADs were diagnosed using clinical and complementary paraclinical findings by an immunologist and/or a subspecialist related to the affected organ or system. Results: We evaluated 50 male and 42 female PID patients with a mean age of 40.92 (18-86). Twenty-nine (32 %) patients (15 females/14 males) with a mean age of 43.8 (19-78) had ADs. In our study group, the most commonly detected type of PID with AD is common variable immune deficiency (CVID) (n=17); followed by combined immune deficiency (CID) (n=3), CTLA4 deficiency (n=2), selective IgA deficiency (sIgAD) (n=2), specific IgG subgroup deficiency (n=1), autoimmune polyglandular syndrome (APS) with hypogammaglobulinemia (n=1), dyskeratosis congenita (DC) (n=1), Osler-Rendu-Weber (ORW) syndrome with CVID-like PID (n=1), and cartilage-hair hypoplasia (CHH) (n=1). According to systematic assessments, ADs resulted in endocrinologic 14%, dermatologic 10.8%, rheumatologic 9.7%, gastroenterological 9.7%, hematological 8.6%, and neurologic disorders 1%. The frequency of ADs was higher in CVID cases than other types of PIDs (p <0.05). Basic and immunologic laboratory findings of the PIDs with and without ADs were analyzed and compared; however, no statical significant difference was obtained between the groups. Conclusion: We have analyzed the frequency and variety of ADs in a adult PID cohort in Turkey. Patients presenting with multiple ADs should be screened for having an underlying PID. Keywords: Primary immune deficiency, autoimmunity, autoantibody, immunologic parameters, frequency


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