Long-term study of a female hyper-IgM immunodeficiency

Hyper-IgM immunodeficiency (HIM) is an immunological disorder characterized by normal or elevated serum IgM levels, and reduced serum IgG and IgA leve ls, due to the disruption of immunoglobulin class switching in B cells. X-l inked hyper-IgM is caused by the defective expression of the CD40 ligand on activated T cells, which induces immunoglobulin class switching along with some cytokines, such as interleukin 4, by the signal transduction of CD40 in B cells. We report on a Japanese girl who initially showed low serum IgM , IgG and IgA levels like patients with common variable immunodeficiency; h owever, in the course of time, serum IgG levels became reduced and serum Ig M levels increased, resulting in the typical immunoglobulin profile of HIM. Neutropenia, one of the features of X-linked HIM, was not observed. In spi te of extremely low serum IgG levels, she did not show any predisposition t o severe infection, even without gammaglobulin replacement therapy. No muta tion of the CD40 ligand or CD40 was detected. Sequencing of the complementa rity-determining region of immunoglobulin heavy-chain genes in peripheral B lymphocytes revealed that they were all in frame, and insertion of the N r egion was detected. These results indicate that the heavy-chain gene rearra ngement in the patient's B cells is intact. Non-X-linked HIM has heterogene ous pathogenetic mechanisms, and some groups may show the resistance to inf ection at the healthy donor level. The underlying defects in non-X-linked H IM might be specifically involved in class switching. Copyright (C) 2000 S. Karger AG. Basel.