The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3+TCRαβ+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3+T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.

Additional Metadata
Persistent URL dx.doi.org/10.1111/sji.12200, hdl.handle.net/1765/89102
Journal Scandinavian Journal of Immunology
Citation
Göktürk, B, Keles, S, Kirac, M, Artac, H, Tokgoz, H, Guner, S.N, … Reisli, I. (2014). CD3G gene defects in familial autoimmune thyroiditis. Scandinavian Journal of Immunology, 80(5), 354–361. doi:10.1111/sji.12200