Heemskerk M B A, Cornelissen J J, Roelen D L, van Rood J J, Claas F H J, Doxiadis I I N, Oudshoorn M
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Bone Marrow Transplant. 2007 Aug;40(3):193-200. doi: 10.1038/sj.bmt.1705721. Epub 2007 May 28.
A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor-recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the alpha-helices plus five or more differences in the beta-sheet (> or =5alpha5beta) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a > or =5alpha5beta mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03-0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.
对于大多数需要进行造血干细胞移植（SCT）的患者来说，完全匹配主要组织相容性复合体（MHC）的供体并不存在，这表明需要一种工具来界定可接受的MHC差异。此前，我们注意到，如果MHC氨基酸序列在α螺旋中有五个或更多差异，并且在β折叠中有五个或更多差异（≥5α5β），那么多种单MHC I类错配的异基因供体-受体对在体外不会引发异基因细胞毒性淋巴细胞（CTL）反应（7）。为了探讨这一观察结果的临床相关性，我们分析了53名接受来自无关供体的单MHC I类错配移植物的荷兰受者的CTL前体（CTLp）检测结果和SCT结果。4年后患者总体生存率为44%。在多变量分析中，移植前体外CTLp频率为阴性的≥5α5β错配移植物受者显示出更高的生存率：4年生存率为80%，而其他CTLp频率为阴性的错配移植物受者的4年生存率为47%（风险比=0.131；95%置信区间=（0.03 - 0.61）；P = 0.009）。这种可接受错配的选择可能会扩大潜在可接受的干细胞供体库。
