Vidan-Jeras B, Buhler S, Dubois V, Grubic Z, Ivanova M, Jaatinen T, Ligeiro D, Lokki M-L, Papasteriades C, Poli F, Spyropoulou-Vlachou M, Tordai A, Viken M K, Wenda S, Nunes J M, Sanchez-Mazas A, Tiercy J-M
Tissue Typing Center, Blood Transfusion Center of Slovenia, Ljubljana, Slovenia.
Tissue Antigens. 2014 Nov;84(5):459-64. doi: 10.1111/tan.12422. Epub 2014 Sep 11.
Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B44:02:01G, DRB114:01:01G and DQB103:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB114:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB114:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B44:02/44:27 ambiguity showed that B44:27 had a high relative ratio in Slovenians (25.5%) and Bulgarians (37%) and low in French and Swiss (0.02-1%), and was not observed in Greeks and Italians. The highest relative ratio of DQB103:19 was found in Portuguese (11%), by contrast with low ratios (0-3%) in the other five populations. Analysis of the A, B, DRB1 phenotypes and family-derived haplotypes in 1719 and 403 individuals positive for either HLA-B44:02G or DRB114:01G ambiguities, respectively, showed some preferential associations, such as A26∼DRB114:01, B35∼DRB114:01, B38∼DRB114:01 and B44:27∼DRB116. Because these ambiguities are located outside the peptide-binding site, they may not be recognized by alloreactive T-cells. However, because of strong linkage disequilibrium (LD), the DRB114:01 vs DRB114:54 and the B44:02 vs B44:27 mismatches are associated to DRB3-, and C-mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For B*44:27-positive patients, searches are expected to be more successful when requesting donors from Southeastern-European ancestry. Furthermore, the introduction of human leukocyte antigen (HLA)-typing strategies that allow resolving exon 4 (for class I) and exon 3 (for class II) polymorphisms can be expected to contribute significantly to population genetics studies.
在欧盟资助的HLA-NET行动框架内，对12个欧洲人群中的三个G组等位基因HLA-B44:02:01G、DRB114:01:01G和DQB103:01:01G进行了分析。通过聚合酶链反应-序列特异性扩增（PCR-SSP）或基于序列的PCR分型（PCR-SBT）解决了总共5095名个体中的模糊性问题。DRB114:01/14:54模糊性的结果显示，保加利亚人、克罗地亚人、希腊人、意大利人和斯洛文尼亚人中DRB114:01的相对比例较高（24%-53%），而奥地利人、芬兰人、法国人、匈牙利人、挪威人和瑞士人中的比例较低（6%-13%）。B44:02/44:27模糊性的解决表明，B44:27在斯洛文尼亚人（25.5%）和保加利亚人（37%）中的相对比例较高，在法国人和瑞士人中较低（0.02%-1%），在希腊人和意大利人中未观察到。DQB103:19的最高相对比例在葡萄牙人中发现（11%），而在其他五个人群中的比例较低（0%-3%）。对分别为HLA-B44:02G或DRB114:01G模糊性阳性的1719名和403名个体的A、B、DRB1表型和家族衍生单倍型进行分析，发现了一些优先关联，如A26∼DRB114:01、B35∼DRB114:01、B38∼DRB114:01和B44:27∼DRB116。由于这些模糊性位于肽结合位点之外，它们可能不会被同种异体反应性T细胞识别。然而，由于强连锁不平衡（LD），DRB114:01与DRB114:54以及B44:02与B44:27的错配分别与DRB3-和C-错配相关。这些结果对于搜索无关造血干细胞供体的算法具有参考价值。对于B*44:27阳性患者，当从东南欧血统的人群中请求供体时，搜索预计会更成功。此外，引入能够解决外显子4（I类）和外显子3（II类）多态性的人类白细胞抗原（HLA）分型策略有望对群体遗传学研究做出重大贡献。
