Cellular and Molecular Characterisation of the Hyper Immunoglobulin M Syndrome Associated with Congenital Rubella Infection

The hyper-immunoglobulin M syndrome (HIM) is a rare group of immune deficiency disorders characterised by normal or increased serum IgM with normal or reduced IgG, IgA and IgE. We have undertaken detailed cellular and molecular studies in a 53-year-old man with HIM as a result of congenital rubella. No mutations were detected in the CD40 ligand, activation-induced cytidine deaminase and uracil DNA glycosylase. His T-cell responses to lectins and antigens were normal. Flow cytometry confirmed the presence of CD40 ligand on activated T cells. Most CD40-dependent functions that were tested, including B-cell proliferation, isotype switching and production of memory B cells, were normal. CD40/IL4 dependent rescue from anti-IgM-induced apoptosis was impaired. The detection of cell-surface IgG but lack of serum IgG indicated that he may have an antibody secretion defect.