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HLA-B51 and haplotypic diversity of B-Cw associations: implications for matching in unrelated hematopoietic stem cell transplantation

Bettens, F.
Nicoloso de Faveri, G.
Published in Tissue Antigens. 2009, vol. 73, no. 4, p. 316-325
Abstract 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.
Keywords *Genetic VariationGenetics, PopulationGenotypeHLA-B Antigens/*geneticsHLA-B51 AntigenHLA-C Antigens/geneticsHaplotypes/*genetics*Hematopoietic Stem Cell TransplantationHistocompatibility TestingHumansMicrosatellite RepeatsRegistriesTissue Donors
PMID: 19317740
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Research group Compatibilité tissulaire et transplantation clinique (562)
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BETTENS, F., NICOLOSO DE FAVERI, G., TIERCY, Jean-Marie. HLA-B51 and haplotypic diversity of B-Cw associations: implications for matching in unrelated hematopoietic stem cell transplantation. In: Tissue Antigens, 2009, vol. 73, n° 4, p. 316-325. https://archive-ouverte.unige.ch/unige:19679

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Deposited on : 2012-04-23

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