The epidemiology and clinical feature of selective immunoglobulin a deficiency of Zhejiang Province in China.

BACKGROUND: Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency disease and frequently reported in the Western countries. However, large-scale epidemiologic studies on SIgAD in China are still lacking. METHODS: The clinical information of 555 180 subjects (age >4 years) including the outpatient, inpatient, and healthy subjects who had ordered serum immunoglobulin A, G, M in 9 hospitals of Zhejiang Province in China was collected. The SIgAD individuals were defined as IgA level <0.07 g/L with normal levels of serum IgG and IgM, whose age should be over 4 years, and any other secondary diseases causing SIgAD were also excluded. Then, the geographical and prevalence distribution of SIgAD individuals in Zhejiang Province and patients' clinical characteristics at the time of diagnosis were also reviewed. RESULT: Among these 555 180 subjects who had ordered the immunoglobulin evaluation, the prevalence of SIgAD was 109/555180 (0.02%). The ratio of male to female of these SIgAD individuals was 1:1.37, which also included 87 adults (≥18 years) and 22 children (18 > age >4 years). For adults, the common clinical features were infections (43/87, 49.43%), autoimmune disorders (31/87, 35.63%), allergic cases (5/87, 5.75%), and tumor cases (4/87, 4.60%). Additionally, infectious diseases (20/22, 90.91%), autoimmune disorders (4/22, 18.18%), and allergic cases (1/22, 4.55%) were found in 22 children. CONCLUSION: We first describe a large cohort of SIgAD individuals of Zhejiang Province in China. The incidence was 0.020%. The common clinical features were infection, autoimmune disorders, tumor, and allergy, and the infection rate was higher in children than the adults.

Common variable immunodeficiency-associated endotoxemia promotes early commitment to the T follicular lineage.

BACKGROUND: Although chiefly a B-lymphocyte disorder, several research groups have identified common variable immunodeficiency (CVID) subjects with numeric and/or functional TH cell alterations. The causes, interrelationships, and consequences of CVID-associated CD4+ T-cell derangements to hypogammaglobulinemia, autoantibody production, or both remain unclear. OBJECTIVE: We sought to determine how circulating CD4+ T cells are altered in CVID subjects with autoimmune cytopenias (AICs; CVID+AIC) and the causes of these derangements. METHODS: Using hypothesis-generating, high-dimensional single-cell analyses, we created comprehensive phenotypic maps of circulating CD4+ T cells. Differences between subject groups were confirmed in a large and genetically diverse cohort of CVID subjects (n = 69) by using flow cytometry, transcriptional profiling, multiplex cytokine/chemokine detection, and a suite of in vitro functional assays measuring naive T-cell differentiation, B-cell/T-cell cocultures, and regulatory T-cell suppression. RESULTS: Although CD4+ TH cell profiles from healthy donors and CVID subjects without AICs were virtually indistinguishable, T cells from CVID+AIC subjects exhibited follicular features as early as thymic egress. Follicular skewing correlated with IgA deficiency-associated endotoxemia and endotoxin-induced expression of activin A and inducible T-cell costimulator ligand. The resulting enlarged circulating follicular helper T-cell population from CVID+AIC subjects provided efficient help to receptive healthy donor B cells but not unresponsive CVID B cells. Despite this, circulating follicular helper T cells from CVID+AIC subjects exhibited aberrant transcriptional profiles and altered chemokine/cytokine receptor expression patterns that interfered with regulatory T-cell suppression assays and were associated with autoantibody production. CONCLUSIONS: Endotoxemia is associated with early commitment to the follicular T-cell lineage in IgA-deficient CVID subjects, particularly those with AICs.

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood.

Transient hypogammaglobulinaemia of infancy (THI) is a relatively rare disorder where there is an exaggeration of the physiological nadir of immunoglobulin (Ig)G between loss of transplacentally acquired maternal IgG and production by the infant. Patients may be vulnerable to infections during the period of hypogammaglobulinaemia. The precise time to recovery in all infants is currently unknown. We sought to determine the clinical features and time-course of recovery for patients with THI. We reviewed our experience with THI over the last three decades in order to describe clinical and laboratory features, as well as the time-course of recovery. Forty-seven patients were identified with THI. Only thirty-seven per cent remitted by 4 years of age, while some patients did not recover until the third or fourth decade. In keeping with previous studies, the majority (25 of 47) presented with recurrent infections, nine had a family history of immunodeficiency and 13 had adverse reactions to food as their dominant clinical manifestation. Chronic tonsillitis developed in 10 patients and symptoms improved following surgery. The group with food allergies recovered sooner than those presenting with infections or with a family history immunodeficiency. Eight patients failed to respond to at least one routine childhood vaccine. Two have IgA deficiency and four individuals recovering in adolescence and adulthood continue to have borderline/low IgG levels. None have progressed to common variable immunodeficiency disorders (CVID). THI is a misnomer, as the majority do not recover in infancy. Recovery from THI can extend into adulthood. THI must be considered in the differential diagnosis of adolescents or young adults presenting with primary hypogammaglobulinemia.

Oral manifestations of selective IgA-deficiency: review and case-report.

Immunoglobulin A deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA (less than 7 mg/dl) 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, allergic disorders and autoimmune manifestations, such as diabetes mellitus, Graves disease and celiac disease. The international literature has not produced any kind of review yet about intra-oral manifestations of selective IgA-deficiency. L.S., a 7-year-old Caucasian girl, was examined at our hospital. After she had undergone a professional dental cleaning, a symmetric, bilateral ulcerative gingivitis developed nearby the upper second primary molars. The gingival ulcers were persistent and did not disappear in the following 3 weeks. In the meantime, the young patient reported the presence of gastrointestinal symptoms. IgA serum level was 4.5 mg/dl, while the other isotypes levels were in the common range. The diagnosis of selective IgA-deficiency was formulated and the girl underwent further examination for the specific IgG autoantibodies in celiac disease, which were not present. Consequently, a full prevention program was planned. This case report emphasizes the role of the paediatric dentist in the early detection of systemic disorder, such as the immunological diseases. The oral cavity often reveals to be the first site of manifestation of important systemic diseases. Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency and is defined as a decrease in serum IgA levels in the presence of normal levels of other immunoglobulin isotypes (1). Serum IgA deficiency was first described in children with ataxia-telangiectasia (2) and has since been identified in other patients, including normal patients. The prevalence of IgA deficiency ranges from 1:223 to 1:1000 in community studies and from 1:400 to 1:3000 in healthy blood donors (3).

Association between IgA deficiency & other autoimmune conditions: a population-based matched cohort study.

PURPOSE: To examine autoimmune disorders in patients with IgA deficiency compared with the general population. METHODS: Nationwide prospective population-based cohort study. Through six university hospitals in Sweden we identified 2100 individuals with IgA deficiency (IgA levels < .07 g/L) diagnosed between 1980 and 2011. Each patient with IgA deficiency was matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls (n = 18,653). Data on nine autoimmune disorders were retrieved from the Swedish National Patient Register (including inpatient and non-primary outpatient care). Autoimmune disorders were defined as having at least two visits listing the relevant international classification of disease (ICD) code as main diagnosis. Prevalences and prevalence ratios (PRs) were calculated. RESULTS: Individuals with IgA deficiency more often had celiac disease (6.7 % vs. 0.19 % in controls) and type 1 diabetes (5.9 % vs. 0.57 %) corresponding to a 35-fold higher PR for celiac disease and 10-fold higher for type 1 diabetes. Also for the other autoimmune diseases did we see statistically significantly elevated prevalences and PRs (juvenile idiopathic arthritis (0.76 % vs. 0.09 % in controls, PR = 8.9), systemic lupus erythematosus (0.57 % vs. 0.06 %; PR = 8.9), inflammatory bowel disease (3.9 % vs. 0.81 %; PR = 5.0; specifically Crohn's disease (2.4 % vs. 0.42 %; PR = 5.7) and ulcerative colitis (1.7 % vs. 0.46 %; PR = 3.9)), hypothyreosis (0.76 % vs. 0.16 %; PR = 4.6), rheumatoid arthritis (2.2 % vs. 0.50 %; PR = 4.5), and hyperthyreosis (1.7 % vs. 0.43 %; PR = 3.9), but not with myasthenia gravis (0.05 % vs. 0.02 %; PR = 3.0). CONCLUSIONS: Individuals with IgA deficiency have a higher prevalence of several other autoimmune disorders.

Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities.

BACKGROUND: Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25(high)forkhead box P3 (FoxP3)+ regulatory T cells (T(reg)) have been shown in association with autoimmune and inflammatory disorders. METHODS: In order to evaluate the relationship between autoimmunity and T(reg) in SIgAD, we studied 26 IgA-deficient patients (aged 4-17 years) with serum IgA levels <7 mg/dl, 26 age- and sex-matched healthy controls and 26 age- and sex matched idiopathic thrombocytopenic purpura cases with normal immune system. T(reg) were determined by flow cytometry using T(reg) markers, including CD4, CD25 and FoxP3. RESULTS: The mean percentage of CD4, CD25+FoxP3+ T(reg) from all CD4+ cells was 4.08 ± 0.86 in healthy controls, which was significantly higher than in SIgAD patients (2.93 ± 1.3; p = 0.003). We set a cutoff point (2.36%) for T(reg), which was two standard deviations lower than the mean of normal controls. According to this cutoff point and in order to assess the role of T(reg) in clinical SIgAD manifestation, we classified patients into two groups: 16 patients in G1 with T(reg) <2.36% and 10 patients in G2 with T(reg) >2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). CONCLUSION: This study showed decreased proportions of T(reg) in SIgAD patients, particularly in those with signs of chronic inflammation.

Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?

AIMS: Immunoglobulin A (IgA) measurement is advocated when case finding for coeliac disease in patients with Type 1 diabetes mellitus. Currently, there is a paucity of contemporary studies assessing IgA deficiency in Type 1 diabetes. This study evaluates the prevalence of IgA deficiency in individuals with Type 1 diabetes, compared with patients with coeliac disease and control subjects. In addition, we evaluate whether routine IgA measurement is justifiable when case finding for coeliac disease in patients with Type 1 diabetes. METHODS: All patients were assessed using IgA endomysial antibodies, IgA anti-tissue transglutaminase antibodies and total IgA levels. Altogether, 2434 individuals were tested: 1000 patients with Type 1 diabetes, 234 patients with coeliac disease and 1200 population control subjects. Definitive IgA deficiency was defined as total IgA levels < 0.07 g/l. RESULTS: The prevalence of IgA deficiency was significantly more common in patients with Type 1 diabetes (0.9%, n = 9/1000; P = 0.036) and coeliac disease (1.29%, n = 3/234; P = 0.041) when compared with population control subjects (prevalence of 0.17%, 2/1200). No statistical difference between Type 1 diabetes and coeliac disease for IgA deficiency was identified (P = 0.87). Of patients in the group with Type 1 diabetes, 3.3% (33/1000) had coeliac disease, and of those only one patient had IgA deficiency leading to an antibody-negative presentation. Both IgA-deficient individuals within the population control subjects had normal duodenal biopsies and no relevant symptoms. CONCLUSIONS: IgA deficiency is more common in Type 1 diabetes compared with population control subjects. Despite this, very few individuals with Type 1 diabetes and IgA deficiency appear to have villous atrophy on biopsy. These outcomes question the practice of routine IgA measurement when case finding for coeliac disease in patients with Type 1 diabetes.

Primary cutaneous marginal zone lymphoma with sequential development of nodal marginal zone lymphoma in a patient with selective immunoglobulin A deficiency.

Multiple lymphoma subtypes occurring within one patient is rare in the context of B-cell lymphoma, and only few such cases have been reported in association with primary cutaneous marginal zone lymphoma (PCMZL). We herein describe the case of a 43-year-old patient who was diagnosed with PCMZL and subsequently developed a clonally unrelated nodal marginal zone lymphoma (MZL). At the time of diagnosis of PCMZL, multiple skin lesions were present. The atypical lymphoid infiltrate showed monotypic expression of immunoglobulin light chain lambda and heavy chain (IgM) on immunohistochemistry and an identical B-cell clone. No sign of systemic lymphoma was present in staging examinations. Complete remission was achieved utilizing rituximab. After a 3-year clinical course of repetitive cutaneous relapses and remissions, the patient additionally developed nodal lymphoma involvement by MZL which, however, harbored an immunophenotype and a genetic clone distinct from the cutaneous lymphoma counterpart. Therefore, the rare occurrence of two different types of MZL with sequential evolution was diagnosed. In this uncommon case, we hypothesize that selective immunoglobulin A deficiency may play a promoting role for the metachronous development of the two MZL that occurred in our patient.

B-cell subsets in patients with transient hypogammaglobulinemia of infancy, partial IgA deficiency, and selective IgM deficiency.

BACKGROUND: The pathogenesis of some primary humoral immunodeficiencies, such as transient hypogammaglobulinemia of infancy (THI) and immunoglobulin (Ig) A deficiency, remains unknown and can render diagnosis problematic. OBJECTIVE: In the present study, we used flow cytometry to analyze peripheral blood B-cell subsets in patients with THI and unclassified hypogammaglobulinemia (UCH), partial IgA deficiency, and selective IgM deficiency. METHODS: The study population comprised 41 patients with hypogammaglobulinemia (THI, 18; UCH, 23), 16 patients with partial IgA deficiency, and 16 patients with selective IgM deficiency who were admitted to Ankara University Department of Pediatric Immunology-Allergy between January 2010 and April 2011, as well as 29 healthy controls. B-cell subsets were examined according to the EUROclass classification. RESULTS: Age at diagnosis in the hypogammaglobulinemia group ranged between-14 months and 13 years (median, 26 months). Naive B-cell percentages were significantly higher and activated B-cell values lower in the THI patients than in the UCH patients and age-matched healthy controls. Nonswitched (IgM+CD27+IgD+) memory B-cell values were found to be significantly lower in patients with selective IgM deficiency than in healthy controls. No significant differences in B-cell subsets were found in patients with partial IgA deficiency. CONCLUSIONS: Previous reports show that reduced class-switched memory B cell values are associated with CVID, THI, and selective IgA deficiency. Our findings did not support these reports. Furthermore, we observed that naive B cell values were higher in patients with THI. A maturation defect could play a role in the pathogenesis of THI.

[State of local immunity in herpetic stomatitis patients].

It was set by us, that at intensifying of herpetic stomatititis of mucous membrane of oral cavity for patients the deficit of lysozyme and antibodies of class is marked A in the mixed saliva. At what the degree of expressed of the exposed violations of local immunity correlated with frequency of relapses of viral infection and its duration.

Reversible IgA deficiency after severe Gram-negative bacteria infection in a patient with systemic sclerosis.

A 43-year-old woman with systemic sclerosis (SSc) developed IgA deficiency (IgAD) after cholecystitis. The severe decrease of IgA (<10 mg/dl) partially recovered after 5 years. She had repeated episodes of infection during IgAD. Anti-IgA antibody was not detected. Flow cytometric analysis showed that peripheral CD19(+)IgA(+) and CD38(+)IgA(+) cells were normally present. Although the mechanism of secondary IgAD is still vague, its association with autoimmune diseases including SSc and also with bacterial infection is discussed.

High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency.

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+) IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD.

GLILD Revisited: Pulmonary Pathology of Common Variable and Selective IgA Immunodeficiency.

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.

Generation of human induced pluripotent stem cell lines from patients with selective IgA deficiency.

Selective immunoglobulin-A deficiency (IgAD) is the most common primary immunodeficiency (PID) in the Western world and results in higher susceptibility to infections, autoimmune disorders and malignancies. We generated human induced pluripotent stem cell lines from two patients with selective IgAD, PHAi001 and PHAi002. Patient samples were reprogrammed using non-integrative based methods. Pluripotency of the PHAi001 and PHAi002 cell lines was confirmed by their expression of stem cell markers and capacity to differentiate into cells of the three germ layers. The PHAi001 and PHAi002 lines are a unique resource for experimental modeling of selective IgAD and associated disorders.

Necrotizing vasculitis with a polyarteritis nodosa-like pattern and selective immunoglobulin A deficiency: case report and review of the literature.

Selective immunoglobulin A deficiency (IgAD) is a primary immunodeficiency disease characterized by low levels (< 7 mg/dl) of serum immunoglobulin (Ig) A and normal serum levels of IgG and IgM. Patients with IgAD have increased risk for recurrent respiratory and gastrointestinal infections, autoimmune disease, asthma and allergy. A 26-year-old woman was admitted with sudden onset of painful cutaneous lesions on her lower extremities, pyrexia and arthromyalgia. Her medical history was remarkable for recurrent respiratory tract infections, self-limited episodes of acute diarrhea, atopy, splenomegaly and a 4-year history of a lung granulomatous lesion. Laboratory and imaging tests ruled out severe life-threatening infection, connective tissue disease and neoplasm. Serum protein electrophoresis showed a low IgA serum level (6.67 mg/dl), with normal serum levels of IgG and IgM, conducting to a diagnosis of selective IgAD. A skin biopsy showed necrotizing vasculitis without any sign of internal organ disease. We report a patient with IgAD and granulomatous involvement of lungs, spleen and medium-sized arteries of the skin. Although IgAD results from a failure of B-cell differentiation, we propose that deregulated immune response with production of cross-reactive antibodies and hyperstimulation of T cells and macrophages could contribute to this widespread granulomatous reaction.

Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.

Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation-inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributed to early antibacterial defense against P. aeruginosa. Consequently, P. aeruginosa-binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substitute. Our study provides a mechanistic explanation for the well-documented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy.

The clinical significance of immunoglobulin A deficiency.

IgA deficiency is the most common primary immunoglobulin deficiency. The prevalence in Caucasians is around one in 500, whereas in some Asian populations it is very uncommon. Most individuals with IgA deficiency are clinically asymptomatic. Those with symptoms of immunodeficiency have predominantly sinopulmonary or gastrointestinal infections, which are more severe when associated with IgG2, IgG4 or specific antibody deficiency. IgA deficiency is believed to be one end of a spectrum of immunodeficiency with common variable immunodeficiency at the most severe end. Although primary IgA deficiency is the most commonly encountered form, secondary deficiencies due to drugs or viral infections are recognized. IgA deficiencies can be partial or transient. Primary IgA deficiency is caused by a defect of terminal lymphocyte differentiation, which leads to underproduction of serum and mucosal IgA; affected individuals have normal IgA genes. A number of non-immunoglobulin genes have been implicated in IgA deficiency. There have been many diseases reported in association with IgA deficiency, particularly autoimmune diseases. The most common association is with coeliac disease (CD), which has special significance since CD is usually diagnosed by detection of specific IgA antibodies that are obviously lacking in IgA deficiency. There is no specific treatment for patients with symptomatic IgA deficiency. Antibiotics are prescribed in those with acute infections. A significant proportion of IgA-deficient individuals are reported to have anti-IgA antibodies in their serum. Although blood or blood products given to IgA-deficient individuals can lead to severe, even fatal, transfusion reactions, such reactions are rare.

Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency.

Common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD) are the most common primary immunodeficiencies in human. Both diseases share clinical manifestation and molecular defects. Increased apoptosis may be one of the mechanisms involved in the pathogenesis of CVID and SIgAD. Elevated apoptosis in this disorder leads to defective long-term survival of B-cells, reduced antibody production, decreased lymphocyte proliferation and defective cytokine secretion. For the first time, we reviewed the role of apoptosis in CVID and SIgAD.

Clinical phenotype classification for selective immunoglobulin A deficiency.

Selective immunoglobulin A deficiency (SIgAD) is the most common predominantly antibody deficiency, with a wide range of presentations from asymptomatic to severe manifestations. Although many studies have investigated different aspects of SIgAD, no study has yet presented a comprehensive classification of this disease. Based on clinical manifestation of patients and various immune abnormalities associated with SIgAD, this group of patients could be classified into five different phenotypes including asymptomatic, minor infectious, allergic, autoimmune and severe phenotypes. This classification aids physicians in identifying patients and in choosing appropriate management and treatment as well as homogenized groups for molecular and genetic studies.