Title | Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Jain A, Kovacs JA, Nelson DL, Migueles SA, Pittaluga S, Fanslow W, Fan X, Wong DW, Massey J, Hornung R, Brown MR, Spinner JJ, Liu S, Davey V, Hill HA, Ochs H, Fleisher TA |
Journal | Blood |
Volume | 118 |
Issue | 14 |
Pagination | 3811-7 |
Date Published | 2011 Oct 06 |
ISSN | 1528-0020 |
Keywords | Adolescent, Animals, CD40 Ligand, Child, Follow-Up Studies, Humans, Hyper-IgM Immunodeficiency Syndrome, Type 1, Immunotherapy, Interferon-gamma, Lymph Nodes, Mice, Recombinant Proteins, T-Lymphocytes, Tumor Necrosis Factor-alpha |
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. |
DOI | 10.1182/blood-2011-04-351254 |
Alternate Journal | Blood |
PubMed ID | 21841160 |
PubMed Central ID | PMC3193261 |
Grant List | N01CO12400 / CA / NCI NIH HHS / United States N01-CO-12400 / CO / NCI NIH HHS / United States / / Intramural NIH HHS / United States |
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