B-Cell Mutation Can Cause Hypogammaglobulinemia
Mutation in CD19 gene causes impaired signaling through B-cell receptor
WEDNESDAY, May 3 (HealthDay News) -- Mutations in the gene that codes for the B-cell surface protein CD19 can cause hypogammaglobulinemia due to impaired signaling through the B-cell receptor, according to a study in the May 4 issue of the New England Journal of Medicine.
Jacques J.M. van Dongen, M.D., Ph.D., of Erasmus MC in Rotterdam, the Netherlands, and colleagues studied four patients with hypogammaglobulinemia from two unrelated families. Patient 1 was a 10-year-old girl with intermittent hematuria and a history of recurrent bronchiolitis, bronchopneumonia and meningitis. Patients 2, 3 and 4 were 35, 33 and 49 years old, respectively, from the same family, and had a history of bacterial conjunctivitis, upper respiratory tract infections, otitis media, sinusitis and pharyngitis.
All four patients had a homozygous mutation in the CD19 gene, with undetectable levels of surface protein in one patient and substantially decreased levels in the other three patients. CD19 is part of a complex of proteins that together with the B-cell antigen receptor lowers the threshold for activation by an antigen, the authors note. The patients had normal numbers of B cells, but few were able to switch from one immunoglobulin class to another. Stimulation through the B-cell receptor as well as the antibody response after rabies vaccination was also impaired. Intravenous immune globulin was an effective treatment, according to the study.
"Mutation of the CD19 gene causes a type of hypogammaglobulinemia in which the response of mature B cells to antigenic stimulation is defective," van Dongen and colleagues conclude.