Dorak M T, Chalmers E A, Sproul A M, Mills K I, Wilson D W, Galbraith I, Henderson N, Gibson B E, Burnett A K
Department of Haematology, Glasgow Royal Infirmary, UK.
Bone Marrow Transplant. 1993 Jan;11(1):37-41.
Current practice for the selection of unrelated donors involves serological typing of HLA-A, -B and -DR antigens, DNA analysis of the class II region and the MLR. However, even after matching for the class II loci at the DNA level, a significant proportion of matched unrelated pairs remain MLR reactive. Ideal matching for BMT would be a match for the whole MHC haplotype rather than individual HLA loci. In the present study, we have evaluated the complementary role of class III typing in determining MHC identity. A group of 86 donor/recipient pairs, of which 14 were unrelated, was investigated using C4, Bf, HSP70 and TNF DNA probes. Phenotypically HLA-matched siblings were always identical at the C4 locus which is the most polymorphic of all the loci examined. Nine of the 14 HLA serologically matched MLR non-reactive (RRI < 20%) unrelated pairs had class III mismatching. Four of these pairs with class III mismatching were matched at the DRB and DQB loci by RFLP analysis. These results demonstrate that serological identity, DRB/DQB RFLP-matching and a negative MLR do not always match the whole haplotype in unrelated pairs. It can be concluded that the linkage of the class III loci to both HLA regions makes this region a reliable marker of the whole MHC haplotype.
目前选择无关供者的做法包括对HLA - A、- B和 - DR抗原进行血清学分型、对II类区域进行DNA分析以及进行混合淋巴细胞反应（MLR）。然而，即使在DNA水平上对II类基因座进行匹配后，仍有相当比例的匹配无关供受者对的MLR呈阳性反应。骨髓移植的理想匹配是整个主要组织相容性复合体（MHC）单倍型匹配，而不是单个HLA基因座匹配。在本研究中，我们评估了III类分型在确定MHC同一性方面的补充作用。使用C4、Bf、HSP70和TNF DNA探针研究了一组86对供者/受者，其中14对为无关供受者。表型上HLA匹配的同胞在C4基因座上总是相同的，C4基因座是所有检测基因座中多态性最高的。14对HLA血清学匹配且MLR无反应（反应率指数 < 20%）的无关供受者对中有9对存在III类错配。通过限制性片段长度多态性（RFLP）分析，这9对中4对III类错配的供受者对在DRB和DQB基因座上是匹配的。这些结果表明，血清学同一性、DRB/DQB RFLP匹配以及阴性MLR在无关供受者对中并不总是与整个单倍型匹配。可以得出结论，III类基因座与两个HLA区域的连锁使得该区域成为整个MHC单倍型的可靠标志物。
