CLINICAL SPECTRUM OF X-LINKED HYPER-IGM SYNDROME

We report the clinical and immunologic features and outcome in 56 pati ents with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrh ea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associat ed with oral and rectal ulcers. The marked prevalence of infections ca used by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro prolif eration to mitogens were normal, a defective in vitro proliferative re sponse to antigens was observed in some patients, and additional defec ts of cell-mediated immunity may be presumed on the basis of current k nowledge of CD40-ligand function. All patients received regular infusi ons of immunoglobulins. Four patients underwent liver transplantation, because of sclerosing cholangitis, which relapsed in three. Three pat ients underwent bone marrow transplantation. Thirteen patients (23%) d ied of infection and/or liver disease. X-linked hyper-IgM syndrome, on ce considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mor tality rate.