Resolution of HLA‐B*44:02:01G, ‐DRB1*14:01:01G and ‐DQB1*03:01:01G reveals a high allelic variability among 12 European populations. Issue 5 (11th September 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Tissue antigens. Volume 84:Issue 5(2014)
• Page Start: 459
• Page End: 464
• Publication Date: 2014-09-11
• Subjects: Antigens -- Periodicals; Immunological tolerance -- Periodicals; Immunogenetics -- Periodicals; 571.9645
• DOI: 10.1111/tan.12422
• Languages: English
• ISSNs: 0001-2815

Abstract

<abstract abstract-type="main" id="tan12422-abs-0001"> <title>Abstract</title> <p id="tan12422-para-0001">Within the framework of the EU‐funded <italic>HLA‐NET</italic> action, an analysis of three G‐group alleles, <italic>HLA‐B*44:02:01G</italic>, <italic>DRB1*14:01:01G</italic> and <italic>DQB1*03:01:01G</italic>, 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 <italic>DRB1*14:01/14:54</italic> ambiguity showed high relative ratios (24–53%) of <italic>DRB1*14:01</italic> in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6–13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the <italic>B*44:02/44:27</italic> ambiguity showed that <italic>B*44:27</italic> 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 <italic>DQB1*03:19</italic> 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 <italic>HLA‐B*44:02G</italic> or <italic>DRB1*14:01G</italic> ambiguities, respectively, showed some preferential associations, such as <italic>A*26∼DRB1*14:01</italic>, <italic>B*35∼DRB1*14:01</italic>, <italic>B*38∼DRB1*14:01</italic> and <italic>B*44:27∼DRB1*16</italic>. 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 <italic>DRB1*14:01 vs DRB1*14:54</italic> and the <italic>B*44:02 vs B*44:27</italic> mismatches are associated to DRB3‐, and C‐mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For <italic>B*44:27</italic>‐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.</p> </abstract>