Common Variable Immunodeficiency at the End of a Prospering Decade: Towards Novel Gene Defects and Beyond

Hermann Eibel; Ulrich Salzer; Klaus Warnatz


Curr Opin Allergy Clin Immunol. 2010;10(6):526-533. 

In This Article

CD81 Deficiency

Recently, mutations in the CD19 gene were described as a cause for antibody deficiency by the group of van Zelm.[33] CD19 forms a complex together with CD21, CD81, and CD225. The complex lowers the B-cell receptor-signaling threshold by amplifying the BCR signal in response to antigens circulating at low concentrations or forming an immune complex. Studying a 6-year-old girl of consanguineous parents, who also completely lacked CD19 expression on peripheral B cells, van Zelm et al. [34••] reported now a case of CD81 deficiency caused by a homozygous splice site mutation leading to an aberrantly spliced transcript, which encodes for a truncated, probably unstable, CD81 protein. Not surprisingly, the patient shares immunological features with the CD19-deficient patients like impaired Ca2+ flux after BCR stimulation. However, the patient acquired an acute glomerulonephritis, diagnosed as Henoch–Schönlein purpura, which led to terminal renal damage and also had several episodes of autoimmune thrombocytopenia. The hypogammaglobulinemia affected IgG levels more than IgA and IgM and, in contrast to BAFF-R and CD20 deficiency, vaccination responses both to TT and PnPs were severely impaired.[34••]

Compared with their murine knockout counterparts human CD20 and CD81 deficiencies show more pronounced phenotypes, which, for CD81, may be explained by residual CD19 expression on CD81-deficient mouse B cells.[35–37] This distinctive feature together with other important characteristics of the human and murine BAFF-R, CD20, and CD81 deficiencies have been highlighted in Table 1.

It should be noted that each of these three gene defects is represented by only one consanguineous family each and proof of a definite causal relationship calls for the identification of additional affected families.


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