Gokturk, B., Keles, S., Kirac, M., Artac, H., Tokgoz, H., Guner, S. N., Caliskan, U., Caliskaner, Z., Burg, M., Dongen, J., Morgan, N. V., and Reisli, I.
The patients with CD3 γ 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 CD3 G gene (c.80-1 G> 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 Ig E ( n = 2) and atopic eczema ( n = 2). While CD3+ TCR αβ+ 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. [ABSTRACT FROM AUTHOR]