Immunodeficiency, Common Variable, 5 D81.4

The disease name CVID as an acronym for "Common Variable Immunodeficiency" refers to a group of diseases from the group of"primary immunodeficiency diseases (PID)". CVID is characterized by a more or less pronounced deficiency of the three antibody classes IgG, IgA and IgM. The antibody deficiency leads to recurrent and often severe infections , mainly affecting the ears, sinuses, respiratory tract and skin. In the majority of cases, the diagnosis is not made until the third to fourth decade of life.

Immunodeficiency, Common Variable, 5, is also known as antibody deficiency due to a CD20 defect. It is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections, and inability to elicit an antibody response to antigens.

This immunodeficiency is caused by a frequently variable immunodeficiency due to a homozygous mutation in the CD20 gene(MS4A1 gene) located on chromosome 11q13.

The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the number of circulating B-cells is usually within the normal range, but may be low.

Kuijpers et al (2010) reported on a Turkish girl born to consanguineous parents who developed recurrent respiratory infections and bronchopneumonia at the age of 2 years. At baseline, she had low IgG and IgA levels. At a follow-up of 4 years, she showed normal IgM and IgA levels but low IgG levels. Laboratory tests revealed normal B-cell counts but persistent hypogammaglobulinemia, as well as reduced circulating memory B cells. CD20 was completely absent on the surfacesof B cells. In addition, a reduced frequency of somatic hypermutations in IgG heavy chain genes and impaired T-cell-dependent or -independent IgG antibody formation in vitro were noted. However, the patients' B cells showed normal proliferation and formation of IgM, indicating intact early B cell development. In addition, an IgG response could be generated in vivo after repeated booster immunization with tetanus toxoid. B cells from both parents showed approximately 50% CD20 expression compared with controls. Kuijpers et al (2010) detected a homozygous mutation in the MS4A1 gene (112210.0001) in this patient.

1. Athni TS et al (2023) Hypogammaglobulinemia, late-onset neutropenia, and infections following rituximab. Ann Allergy Asthma Immunol 130:699-712.
2. Furlan A et al (2021) COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge. Front Immunol 12:763412.
3. Kuijpers TW et al (2010) CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest 120: 214-222
4. Wright CM et al (2012) MS4A1 dysregulation in asbestos-related lung squamous cell carcinoma is due to CD20 stromal lymphocyte expression. PLoS One7:e34943.