title: Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand.
abstract: X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell-dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-γ and TNF-α. Intracellular cytokine staining studies showed that both CD4(+) and CD8(+) T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell-immune function in patients with XHM.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. ajain@nih.gov
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: William
authors.initials: W
authors.lastname: Fanslow
authors.forename: Xiying
authors.initials: X
authors.lastname: Fan
authors.forename: Duane W
authors.initials: DW
authors.lastname: Wong
authors.forename: Justin
authors.initials: J
authors.lastname: Massey
authors.forename: Ronald
authors.initials: R
authors.lastname: Hornung
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Spinner
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Victoria
authors.initials: V
authors.lastname: Davey
authors.forename: Harry A
authors.initials: HA
authors.lastname: Hill
authors.forename: Hans
authors.initials: H
authors.lastname: Ochs
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
mesh_terms: D000293:Adolescent; D000818:Animals; D023201:CD40 Ligand / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma