Expansion of a suppressor T-cell population associated with the hyper-IgM syndrome and generalized lymphadenopathy

Immunoglobulin deficiency with increased IgM (hyper-IgM recurrent infection syndrome) is thought to be due to a defect of IgM/IgG isotype switching in B cells. Considerable genetic heterogeneity (X-linked, autosomal dominant or autosomal recessive inheritance, acquired forms) exists. We describe a case of hyper-IgM syndrome associated with massive lymphadenopathy in a 10-year-old girl with normal B-cell function. Absolute and relative increases of T-suppressor cells (CD8+) and a decrease of circulating CD4+ ("helper") cells were observed. The CD4+ cells present were all of the CD45R+ subtype, representing relatively immature ("naive") helper cells. In contrast, the number of CD4+ cells within the lymph nodes was increased. When tested fractionally, the patient's CD8+ cells selectively inhibited synthesis of IgG and IgA by normal B cells, but spared IgM. Normal allogenic T cells could induce IgG and IgA production by the patient's B cells. These findings suggest (a) a state of selective suppression of IgG and IgA synthesis with exclusive production of IgM, and (b) an abnormal recirculation of immature T-helper cells. This case represents a variant of this heterogeneous syndrome resembling the findings in neonatal lymphocytes and can be distinguished from the "adult" form of hyper-IgM syndrome which may be due to defective switch T cells.