An imbalance of naive and memory/effector subsets and altered expression of CD38 on T lymphocytes in two girls with hyper‐IgM syndrome

SUMMARY In this report we evaluated CD4 +  T, CD8 + T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4 + T lymphocyte population, expression of CD38 on T lymphocytes, and CD4 + and CD8 + T cell cytokine production in two girls with hyper‐IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4 + T cell counts were low in both children (patient 1: 214 cells/mm 3 and patient 2: 392 cells/mm 3 ), and the CD4/CD8 T cell ratio was 0·4 for patient 1, the patient with the more severe disease, and 1·4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm 3 ) and borderline (286 cells/mm 3 ) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA +  27 +  (naive) CD4 + T lymphocytes being 5·8 and 12·4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)‐ γ and tumour necrosis factor (TNF)‐ α in CD4 + and CD8 + T lymphocytes upon PMA‐Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4 + T lymphocytes and a dramatic redistribution of naive and memory/effector CD4 + T lymphocytes in two girls with non‐X‐linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.