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

B. Vidan-Jeras, S. Buhler, V. Dubois, Z. Grubic, M. Ivanova, T. Jaatinen, D. Ligeiro, M. L. Lokki, C. Papasteriades, F. Poli, M. Spyropoulou-Vlachou, A. Tordai, M. K. Viken, S. Wenda, J. M. Nunes, A. Sanchez-Mazas, Jean Marie Tiercy

Research output: Contribution to journalArticlepeer-review

Abstract

Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B* 44:02:01G, DRB1* 14:01:01G and DQB1* 03:01:01G, 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 DRB1* 14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1* 14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B* 44:02/44:27 ambiguity showed that B* 44:27 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 DQB1* 03:19 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-B* 44:02G or DRB1* 14:01G ambiguities, respectively, showed some preferential associations, such as A* 26~ DRB1* 14:01, B* 35~ DRB1* 14:01, B* 38~ DRB1* 14:01 and B* 44:27~ DRB1* 16. 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 DRB1* 14:01 vs DRB1* 14:54 and the B* 44:02 vs B* 44:27 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.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalTissue Antigens
Volume84
Issue number5
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • B*44:02/44:27
  • DRB1* 14:01/14:54
  • European populations
  • Human leukocyte antigen ambiguities
  • Human leukocyte antigen incompatibilities

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Genetics
  • Medicine(all)

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