Liver Transplantation in a Patient With CD40 Ligand Deficiency and Hyper-IgM Syndrome: Clinical and Immunological Assessments.

Monoclonal antibodies that disrupt CD40–CD40 ligand (CD40L) interactions are likely to have use in human transplantation. However, the extent of the immunosuppressive effects of CD40–CD40L blockade in humans is unknown. Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency syndrome characterized by defects in the CD40–CD40L pathway, severe immune deficiency (IgG), and high or normal IgM levels. However, the effects of CD40L deficiency on T- and natural killer (NK)-cell function is not established. Here, we present a patient with HIGM syndrome who underwent liver transplantation for hepatitis C virus infection. Posttransplantation, NK-cell antibody-dependent cytokine release (γ-interferon) to alloantigens and T cell responses to viral antigens and mitogens were assessed and showed normal CD4+, CD8+, and NK-cell responses. We also examined antibody-dependent cellular cytotoxicity against a CD40+ and HLA-expressing cell line. These experiments confirmed that the patient's NK cells were equivalent to those of normal subjects in mediating antibody-dependent cellular cytotoxicity despite the absence of CD40–CD40L interactions. Mitogenic stimulation of the patient's peripheral blood mononuclear cells showed no expression of CD40L on T and NK cells compared with increased expression in normal subjects. Taken together, these data suggest that absence of CD40L expression is responsible for aberrant B cell immunity but had little impact on NK- and T cell immune responses in vitro.