A novel mutation in CD40 ligand gene in a sporadic patient with hyper-IgM syndrome

Abstract

Hyper-IgM syndrome is a rare immunodeficiency disease characterized by low or absent IgG, IgA, and IgE levels but normal or elevated level of IgM. It can occur as an acquired form or X-linked or autosomal mode of inheritance. The X-linked form (HIGM1) is a result of mutations in the CD40L ligand (CD40L) gene. We investigate the expression of CD40L on activated T cells from a sporadic male case of HIM with no family history and the B cell function in response to anti-CD40L mAb and cytokines. Staining of CD40L on activated T cells from the patient is negative with recently developed anti-human CD40L mAb, M90 and M92. The low expression of CD40L on activated T cells from the patient’s mother is also detected. Sequencing of CD40L coding region reveals a 4 bp deletion within the CD40L binding domain. These results indicate that the patient has X-linked inheritance pattern (XIGM1). CD40L mAb alone could induce the patient’s PBMCs to secret markedly IgG. Our data suggest that the detection of CD40L expression on ativated T cells may be used to identify sporadic cases of HIM as HIGM1.