Immunodeficiency, Common Variable, 5
A number sign (#) is used with this entry because this form of common variable immunodeficiency (CVID), referred to here as CVID5, is caused by homozygous mutation in the CD20 gene (MS4A1; 112210) on chromosome 11q13.
For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Clinical FeaturesKuijpers et al. (2010) reported a Turkish girl, born of consanguineous parents, who developed recurrent respiratory infections and bronchopneumonia at age 2 years. At onset, she had low IgG and low IgA levels. During a follow-up of 4 years, she showed normal IgM and IgA levels, but low IgG levels. Laboratory studies showed normal numbers of B cells, but persistent hypogammaglobulinemia, reduced circulating memory B cells, and complete lack of surface CD20 on B cells. There was also a decreased frequency of somatic hypermutations in IgG heavy chain genes and impaired T cell-dependent or -independent IgG antibody formation in vitro. However, patient B cells showed normal proliferation and formation of IgM, indicating intact early development of B cells. In addition, an IgG response could be generated after repeated booster immunization of tetanus toxoid in vivo. B cells of each parent had about 50% CD20 expression compared to controls.
Molecular GeneticsIn a Turkish girl with common variable immunodeficiency-5, Kuijpers et al. (2010) identified a homozygous mutation in the MS4A1 gene (112210.0001).
Animal ModelKuijpers et al. (2010) found that Cd20-null mice had severely impaired T-cell independent antipolysaccharide antibody responses.