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.
journal_name
Bloodjournal_title
Bloodauthors
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 TAdoi
10.1182/blood-2011-04-351254subject
Has Abstractpub_date
2011-10-06 00:00:00pages
3811-7issue
14eissn
0006-4971issn
1528-0020pii
blood-2011-04-351254journal_volume
118pub_type
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