PMID- 19317740 OWN - NLM STAT- MEDLINE DCOM- 20090529 LR - 20111117 IS - 1399-0039 (Electronic) IS - 0001-2815 (Linking) VI - 73 IP - 4 DP - 2009 Apr TI - HLA-B51 and haplotypic diversity of B-Cw associations: implications for matching in unrelated hematopoietic stem cell transplantation. PG - 316-25 LID - 10.1111/j.1399-0039.2009.01215.x [doi] AB - In unrelated hematopoietic stem cell transplantation (HSCT), human leukocyte antigen (HLA)-C locus incompatibilities occur frequently and are associated with increased risk of posttransplant complications. Because HLA-B51 is associated with a high rate of Cw disparities, we performed a comprehensive four-digit typing analysis of 140 ABCDRB1 B51 genotypes proven by pedigree analysis and 311 unrelated donors selected for 75 B51-positive patients. In addition, 145 A1/Ax-B8/B51-DR3/DRx donors were HLA typed at a high-resolution level and tested for three microsatellite (Msat) polymorphisms located in the HLA class I and III regions. Based on these data sets, 182 different ABCDR haplotypes with 14 different B-Cw associations were detected. Rates of Cw mismatches were shown to be highly correlated with the ABDRB1 haplotypes. We have computed 21 B51 haplotypes that disclose a high probability of HLA-C allele matching and 30 haplotypes with a low (<25%) probability. The HLA-C allele frequency profiles were quite different in these two groups, with a more heterogeneous distribution in the low matching probability group. HLA-Cw*1502 was inversely correlated with the likelihood to identify a Cw-mismatched donor: it was present in 61% of the high vs 18% of the low probability group (P < 0.0001). The analysis of three Msats in the class I and III regions showed a higher allelic diversity in B51-positive haplotypes compared with the conserved A1-B8-DR3 haplotype. HLA-B51 haplotypes therefore exhibit a high diversity at the level of B-Cw associations and of non-HLA polymorphisms in the class I and III regions. Such heterogeneity negatively impacts on overall matching in HSCT. FAU - Bettens, F AU - Bettens F AD - Transplantation Immunology Unit, National Reference Laboratory for Histocompatibility, University Hospital, 24 rue Micheli-du-Crest, Geneva, Switzerland. FAU - Nicoloso de Faveri, G AU - Nicoloso de Faveri G FAU - Tiercy, J-M AU - Tiercy JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (HLA-B Antigens) RN - 0 (HLA-B51 Antigen) RN - 0 (HLA-C Antigens) SB - IM MH - *Genetic Variation MH - Genetics, Population MH - Genotype MH - HLA-B Antigens/*genetics MH - HLA-B51 Antigen MH - HLA-C Antigens/genetics MH - Haplotypes/*genetics MH - *Hematopoietic Stem Cell Transplantation MH - Histocompatibility Testing MH - Humans MH - Microsatellite Repeats MH - Registries MH - Tissue Donors EDAT- 2009/03/26 09:00 MHDA- 2009/05/30 09:00 CRDT- 2009/03/26 09:00 PHST- 2009/03/26 09:00 [entrez] PHST- 2009/03/26 09:00 [pubmed] PHST- 2009/05/30 09:00 [medline] AID - TAN1215 [pii] AID - 10.1111/j.1399-0039.2009.01215.x [doi] PST - ppublish SO - Tissue Antigens. 2009 Apr;73(4):316-25. doi: 10.1111/j.1399-0039.2009.01215.x.