title: Liver Transplantation in a Patient With CD40 Ligand Deficiency and Hyper-IgM Syndrome: Clinical and Immunological Assessments.
abstract: 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.
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: M
authors.initials: M
authors.lastname: Tseng
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: S
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Pediatrics, Division of Immunology, UCLA Center for the Health Sciences, Los Angeles, CA.
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Department of Pediatrics, Division of Immunology, UCLA Center for the Health Sciences, Los Angeles, CA.
authors.forename: C
authors.initials: C
authors.lastname: Kuo
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: J
authors.initials: J
authors.lastname: Choi
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: N N
authors.initials: NN
authors.lastname: Nissen
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: I
authors.initials: I
authors.lastname: Kim
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: M
authors.initials: M
authors.lastname: Chu
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: B
authors.initials: B
authors.lastname: Shin
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.|Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: S C
authors.initials: SC
authors.lastname: Jordan
keywords: clinical research; costimulation; cytotoxicity; hepatology; immune deficiency; immune modulation; immunosuppression; liver transplantation; practice