Hyper IgM syndrome: the other side of the coin.

The hyper IgM syndrome is a rare, inherited immune deficiency disorder resulting from defects in the CD40 ligand/CD40-signaling pathway. X-linked hyper IgM is caused by defects in the CD40 ligand gene that prevent it from delivering an activation signal to antigen-presenting cells via CD40. Over the past year, defects in molecules involved in CD40 signaling have been shown to cause other forms of hyper IgM. These newly identified defects emphasize the importance of interaction between CD40 and its ligand in immunity and the role of these molecules in the pathogenesis of immune deficiency. With genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitively, to perform genetic screening, and to delineate the clinical manifestations of this syndrome. Further research may lead to novel and definitive therapeutic options for patients with hyper IgM syndrome.