IgA deficiency selective type 1 D80.2

Type 1 selective immunoglobulin (Ig) A deficiency (IGAD1) is characterized by decreased or absent serum IgA levels in the presence of normal serum IgG and IgM levels in patients older than 4 years of age in whom other causes of hypogammaglobulinemia have been excluded. IgA in the dimeric form is the dominant immunoglobulin in luminal secretions such as saliva, tears, bronchial secretions, nasal mucosal secretions, and small intestinal mucosal secretions. Individuals with selective IgA deficiency may be asymptomatic or have recurrent sinopulmonary and gastrointestinal infections, allergic diseases, or autoimmune disorders.

IgA is active against several pathogens, including rotavirus, poliovirus, influenza virus, and SARS-CoV-2, protecting the epithelial barrier from pathogens and regulating excessive immune responses in inflammatory diseases. The deficiency of anti-SARS-Cov-2 IgA and secretory IgA (sIgA) could be a possible cause of the severity of COVID-19 infection (Quinti I et al. 2021).

Pedigrees of individuals with IgA deficiency show familial clustering without a clear Mendelian inheritance pattern. Autosomal recessive, autosomal dominant and sporadic inheritance patterns have been observed (Yel, 2010).

The IGAD1 locus is located on chromosome 6p21 (see also IGAD2, the deficiency of IgA2 caused by a mutation in the TNFRSF13B gene (604907) on chromosome 17p11).

Schaffer et al (1989) noted that the clinical consequences of IgA deficiency vary widely. Many affected individuals have no obvious health problems, whereas others may have recurrent infections, gastrointestinal disorders, autoimmune diseases, allergies, or malignancies. A key feature in the pathogenesis of IgA deficiency is an interruption of B-cell differentiation. Affected individuals have normal numbers of IgA-bearing B-cell precursors but a profound deficit in terminal differentiation of IgA-secreting plasma cells. It is likely that selective IgA deficiency and common variable immunodeciency (CVID), defined by reduced levels of one or more Ig classes, represent the polar ends of a clinical spectrum reflecting a common underlying genetic defect (Schaffer et al. 1989).

Hammarstrom and Smith (1999) found that selective IgA deficiency does not result in an increased incidence of infections in approximately two-thirds of cases, whereas the remaining patients suffer from bacterial infections of both the upper and lower respiratory tract. The defect manifests itself already at the stem cell level, and transfer of bone marrow from a donor with IgA deficiency to a normal recipient may result in IgA deficiency in the recipient (Hammarstrom et al., 1985), whereas transfer of bone marrow from a normal individual to a patient with IgA deficiency corrects the defect (Kurobane et al., 1991).

Some patients with IgA deficiency develop anti-IgA antibodies. Van Loghem (1974) reported 2 families with isolated IgA deficiency associated with antibodies to IgA. Anti-IgA antibodies of varying specificity were found in 8 of 15 family members with IgA deficiency; sometimes more than one specificity was observed in the same individual.

Webb and Condemi (1974) found selective IgA deficiency in a 43-year-old woman, offspring of an uncle-niece pairing, with advanced chronic obstructive pulmonary disease. Other immunoglobulins and alpha-1 antitrypsin were normal. Among her relatives, several had either definite or borderline IgA deficiency. Her mother, 71 years old, and 2 brothers, 48 and 44 years old, had emphysema. Buckley (1975) observed familial cases, including 1 family with affected individuals in 3 generations.

In a Swiss kinship, Stocker et al (1968) described selective complete IgA deficiency in 2 sisters, the son and daughter of one and the son of the other. Both parents of the 2 sisters had normal serum globulins. They suspected an autosomal dominant inheritance. Goldberg et al (1968) reported a relationship in which the inheritance appeared to be autosomal recessive. Huntley and Stephenson (1968) reported a large kinship in which autosomal recessive inheritance was suspected, but also reported other families in which dominant inheritance seemed likely.

Ammann and Hong (1971) found inheritance patterns in 5 families suggestive of autosomal inheritance of IgA deficiency, with 4 families having dominant inheritance and 1 family having recessive inheritance.

Grundbacher (1972) concluded that selective immunoglobulin A deficiency is probably multifactorial.

Diagnosis of IgA deficiency depends on measurement of monomeric IgA concentrations in serum; therefore, individuals with IgA deficiency may have IgA in mucous membranes that may provide some protection (review by Yel, 2010).

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