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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bettens, F. Nicoloso de Faveri, G. Tiercy, J-M
Description	Country affiliation: Switzerland Author Affiliation: Bettens F ( Transplantation Immunology Unit, National Reference Laboratory for Histocompatibility, University Hospital, 24 rue Micheli-du-Crest, Geneva, Switzerland.)
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.
File Format	HTM / HTML
ISSN	20592302
Issue Number	4
Volume Number	73
e-ISSN	20592310
Journal	Tissue Antigens
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2009-04-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Genetics Discipline Immunology Genetic Variation Hla-b Antigens Genetics Haplotypes Hematopoietic Stem Cell Transplantation Genetics, Population Genotype Hla-b51 Antigen Hla-c Antigens Histocompatibility Testing Humans Microsatellite Repeats Registries Tissue Donors Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology and Allergy Immunology

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

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