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Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation

Item Type:Article
Title:Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation
Creators Name:Subklewe, M. and Marquis, R. and Choquet, S. and Leblond, V. and Garnier, J.L. and Hetzer, R. and Swinnen, L.J. and Oertel, S. and Papp-Vary, M. and Gonzalez-Barca, E. and Hepkema, B.G. and Schoenemann, C. and May, J. and Pezzutto, A. and Riess, H.
Abstract:BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell responses are focused on the level of EBV antigen and epitope choice depending on the individual human leukocyte antigen (HLA) alleles, we hypothesized that certain HLA alleles or a distinct HLA haplotype may influence the risk of development of PTLD after SOT. METHODS: A multicenter case-control study was performed comparing a group of 155 recipients after SOT with development of PTLD with a group of 1996 recipients after SOT without development of PTLD. Alleles, genotypes, and three locus haplotypes were compared of SOT recipients with and without PTLD. RESULTS: The bivariate analysis showed that carrying HLA-A03 was negatively associated (odds ratio [OR] 0.61, confidence interval [CI] 0.40-0.92, P<0.02) whereas carrying of HLA-B18 (OR 1.79, CI 1.18-2.73, P<0.006) and HLA-B21 (OR 2.08, CI 1.14-3.77, P<0.02) were positively associated with PTLD after SOT. HLA-DR analysis demonstrated a significant negative association between the expression of HLA-DR7 (OR 0.46, CI 0.28-0.78, P<0.004) and PTLD. Three locus haplotype analysis underlined the relevance of a dominant protective effect of HLA-DR7 expression concerning the risk of PTLD development. CONCLUSIONS: Our data suggest an influence of HLA variants on the risk of the development of PTLD. We hypothesize that HLA genes or non-HLA genes within the HLA loci confer a risk modification for the individual patient.
Keywords:Human leukocyte antigen, Solid organ transplantation, Posttransplant lymphoproliferative disease, Epstein-Barr virus
Publisher:Lippincott Williams & Wilkins
Page Range:1093-1100
Date:27 October 2006
Official Publication:https://doi.org/10.1097/01.tp.0000235889.05171.12
PubMed:View item in PubMed

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