Selective deficiency of immunoglobulin A D80.2

Selective immunoglobulin A deficiency (IGAD) is the most common form of primary immunodeficiency (PID), with an incidence of approximately 1 in 600 individuals in the Western world (Cunningham-Rundles 2001).

IgA deficiency is diagnosed when the concentration of serum IgA is <7 mg/dl in patients 4 years of age and older.

IgA occurs in 2 subclasses:IgA1 and IgA2. The ratio IgA1/IgA2=9:1.

IgA deficiency can selectively affect one of both subtypes (selective IgA deficiency):

• ImmunoglobulinA deficiency selective type 1 (mutation in IgAD1).
• Immunoglobulin A deficiency selective, type 2 (mutation in TNFRSF13B)

Since IgA deficiency may be transient in rare cases, repeat measurement after 1-2 months is recommended.

Note: The umbrella term "common variable immunodeficiency"(CVID) refers to a group of diseases characterized by deficiency of all Ig isotypes. Selective IgA deficiency and CVID can occur in the same family.

85-90% of people with IgA deficiency are asymptomatic. Affected individuals with symptomatic, selective immunoglobulin A deficiency suffer from recurrent sinopulmonary and gastrointestinal infections. Furthermore, an increased incidence of lymphatic and non-lymphatic malignancies can be observed in these individuals. There is a higher risk of developing autoimmune diseases in middle age.

IgA is active against various pathogens, including rotavirus, poliovirus, influenza virus and SARS-CoV-2. A deficiency of anti-SARS-Cov-2 IgA and secretory IgA (sIgA) is a possible cause of the severity of COVID-19 infection (Quinti I et al. 2021).

A selective IgA deficiency can also predispose to gastrointestinal diseases and food intolerances, as the first immunological defense in the intestine in the form of secretory IgA is missing. There is therefore an increased prevalence of chronic inflammatory bowel disease or coeliac disease.

Other autoimmune diseases (e.g. thyroiditis, vitiligo, juvenile rheumatoid arthritis (JIA), SLE, type 1 diabetes, dermatomyositis, Sjögren's syndrome, autoimmune hepatitis) also frequently occur together with an IgA deficiency.

Patients with selective IgA deficiency may develop autoantibodies against IgA. These occur in approx. 20-25% of affected patients. Laboratory diagnosis is necessary because in rare cases this can lead to severe anaphylactic reactions and thus to a life-threatening situation when immunoglobulins are administered intravenously (these blood products contain IgA). This also includes blood transfusions.

Selective IgA deficiency (or other associated antibody deficiency syndromes) should be sought in the presence of:

• positive family history for IgA deficiency and/or
• the presence of celiac disease, autoimmune phenomena and an accumulation of infections (upper and lower respiratory tract, gastrointestinal).

In the case of IgA deficiency found by chance or diagnosed specifically, the following should be investigated for clarification as a minimum:

• Differential blood count (IgA, IgG, IgM, IgE)
• IgG subclasses, if applicable
• If necessary, complement diagnostics: AP50,CH50,MB

In the case of proven IgA deficiency, a regular control examination of the immunoglobulins and the IgG subclasses is advisable, at intervals of 2 years. Testing for anti-IgA antibodies is also important, as patients with IgA deficiency and autoantibodies are at increased risk of anaphylaxis for immunoglobulin therapies and blood transfusions. If administration of these products becomes necessary, IgA-depleted preparations can then be used or other precautions taken (e.g., subcutaneous immunoglobulin therapy and avoidance of intravenous administration)

IgA deficiency and CVID (common variable immunodeficiency) are characterized by similar B-cell differentiation disorders, but do not share the same abnormalities of lymphocyte subpopulations. IgA deficiency patients may develop panhypogammaglobulinemia characteristic of CVID.

1. Castigli E et al (2005) TACI is mutant in common variable immunodeficiency and IgA deficiency. Nature Genet 37: 829-834.
2. Cunningham-Rundles C (2001). Physiology of IgA and IgA deficiency. J Clin Immun 21: 303-309.
3. Martin F et al (2005) Unraveling TACIt functions. Nature Genet. 37: 793-795.
4. Quinti I et al (2021) IgA antibodies and IgA deficiency in SARS-CoV-2 infection. Front Cell Infect Microbiol 11:655896.
5. Salzer U et al (2005) Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nature Genet 37: 820-828.