title: Critical function of the CD40 pathway in parvovirus B19 infection revealed by a hypomorphic CD40 ligand mutation.
abstract: Parvovirus B19-induced chronic anemia has been associated with failure to mount an effective neutralizing antibody response. We describe an adolescent male with a 13-year history of parvovirus B19-induced anemia as the primary manifestation of X-linked hyper IgM immunodeficiency (XHIM). This patient, whose serum IgG concentration was at the low end of the normal range and who mounted IgG antibody responses to T cell-dependent antigens, suffered from a nonsense mutation (R11 --> X) in the CD40 ligand (CD40L) gene. This resulted in low-level expression of a mutant CD40L predicted to lack the cytoplasmic domain. Intravenous immunoglobulin therapy alone or in combination with interferon gamma, given in the context of impaired Th1 cytokine production, suppressed but did not eradicate the infection. These results highlight the critical function of the CD40/CD40L pathway in parvovirus B19 infection and suggest that subtle defects in this pathway may underlie cases of chronic parvovirus B19 infection atypical of XHIM.
authors.affiliation: Institute of Transfusion Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Blaeser
authors.forename: Michael
authors.initials: M
authors.lastname: Kelly
authors.forename: Karen
authors.initials: K
authors.lastname: Siegrist
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Storch
authors.forename: Richard S
authors.initials: RS
authors.lastname: Buller
authors.forename: Jessica
authors.initials: J
authors.lastname: Whitlock
authors.forename: Nga
authors.initials: N
authors.lastname: Truong
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
mesh_terms: D000293:Adolescent; D000740:Anemia / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology*; D004359:Drug Therapy, Combination; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D010322:Parvoviridae Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016732:Parvovirus B19, Human / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D017211:Treatment Failure
chemical_list: D007074:Immunoglobulin G; D023201:CD40 Ligand; D007371:Interferon-gamma