Interleukin-2 receptor blockade in cardiac transplantation: influence of HLA-DR locus incompatibility on treatment efficacy
作者:
Katherine Lietz,
Ranjit John,
Ainat Beniaminovitz,
Elizabeth Burke,
Nicole Suciu-Foca,
Donna Mancini,
Niloo Edwards,
Silviu Itescu,
期刊:
Transplantation
(OVID Available online 2003)
卷期:
Volume 75,
issue 6
页码: 781-787
ISSN:0041-1337
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
Background.Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation.Methods and Results.A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA–DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls.Conclusions.IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.
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