Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Foundation, Policlinico San Matteo, Pavia, Italy.
Bone Marrow Transplant. 2011 Jul;46(7):916-22. doi: 10.1038/bmt.2010.246. Epub 2010 Oct 25.
Uncertainty still exists on the role of polymorphisms outside the HLA-DRB1 binding site or inside the HLA-DRB3 binding groove in unrelated hematopoietic SCT (HSCT). The ideal model to solve the conundrum consists of the transplants mismatched for HLA-DRB114:01/14:54 and/or for HLA-DRB302:01/02:02. A task force was set up in Italy to recruit transplanted pairs defined as HLA-DRB114:01 before 2006, the year crucial for the proper definition of the HLA-DRB114:54 allele in molecular biology. Out of 2723 unrelated pairs, 189 transplanted in Italy from 1995 to 2006 were HLA-DRB114:01 positive; 103/189 pairs with good historical DNA were retyped for HLA-DRB114 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB114 and/or HLA-DRB3 mismatched; 99/103, having complete clinical data, underwent statistical analysis for OS, TRM, disease-free survival and acute and chronic GvHD. No significant involvement of HLA-DRB114:01/14:54 or HLA-DRB302:01/02:02 mismatches was found, either alone or combined. Our findings suggest that disparities at exon 3 of the HLA-DRB1 gene seem unlikely to influence the outcome after HSCT. The same may be envisaged for HLA-DRB3()02:01 and (*)02:02 alleles which, although differing in the Ag binding site, seem unable to modulate an appreciable immune response in an HSCT setting.
在非 HLA-DRB1 结合部位或 HLA-DRB3 结合槽内的多态性在无关造血干细胞移植 (HSCT) 中的作用仍存在不确定性。解决这一难题的理想模型包括 HLA-DRB114:01/14:54 和/或 HLA-DRB302:01/02:02 错配的移植。意大利成立了一个工作组，招募了在 2006 年之前定义为 HLA-DRB114:01 的移植对，这一年对于 HLA-DRB114:54 等位基因在分子生物学中的正确定义至关重要。在 2723 对无关供受者中，189 对于 1995 年至 2006 年在意大利进行的移植受者为 HLA-DRB114:01 阳性；103/189 对具有良好的历史 DNA 数据的供受者进行了 HLA-DRB114 和 HLA-DRB3 的高分辨率再分型；31/103 对存在 HLA-DRB114 和/或 HLA-DRB3 错配；99/103 对具有完整临床数据的供受者进行了 OS、TRM、无病生存和急性及慢性 GvHD 的统计分析。单独或联合使用 HLA-DRB114:01/14:54 或 HLA-DRB302:01/02:02 错配均未发现显著影响 HSCT 后的结果。HLA-DRB3()02:01 和 (*)02:02 等位基因也可能如此，尽管它们在抗原结合部位存在差异，但在 HSCT 环境中似乎无法调节明显的免疫反应。
