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

Hermann Eibel; Ulrich Salzer; Klaus Warnatz

Disclosures

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

In This Article

CD20 Deficiency

CD20 forms part of a multimeric protein complex expressed on the cell surface of B cells and is involved in the regulation of Ca2+ transport across the cell membrane.[29,30] CD20 lacks a distinct phenotype and has normal B-cell development and function except diminished Ca2+ responses upon BCR triggering.[31] Its function during B-cell development in humans was now unravelled by Kuijpers et al. [32••] presenting the case of 4-year-old Turkish girl who completely lacked CD20 cell surface expression on B cells. Sequencing of the CD20 gene revealed a homozygous splice site mutation, which abolished expression of normal CD20 mRNA and protein. Although the major lymphocyte subpopulations were normal, the numbers of marginal zone and class switched memory B cells were either reduced or nearly absent. Somatic hypermutation was impaired, Ca2+ responses induced by triggering IgG or IgM and B-cell proliferation were normal. IgG production in vitro was very low, possibly reflecting the paucity of memory B cells in the patient. Over a period of 5 years, the patient's IgA and IgM serum levels were normal, whereas IgG levels were constantly low. Similar to BAFF-R deficiency, T-independent responses against pneumococcal polysaccharides were impaired while T-dependent responses measured upon vaccination with tetanus toxoid were normal. This immune response pattern is reflected by recurrent bronchopulmonary infections on the background of an otherwise normal clinical history. Despite the early onset, the immunological and clinical findings in CD20 deficiency are relatively mild, possibly reflecting more an IgG (subclass) deficiency than full-blown CVID-like antibody deficiency. Therefore, it is not unlikely that other cases of CD20 deficiency, especially those with hypomorphic mutations in CD20, might be found in cohorts of patients with low IgG serum levels, in IgG subclass deficiencies and in patients lacking PnPs specific antibody responses.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....