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

Marion Subklewe*, Rene Marquis, Sylvain Choquet, Veronique Leblond, Jeanne-Luce Garnier, Roland Hetzer, Lode J. Swinnen, Stephan Oertel, Matthias Papp-Vary, Eva Gonzalez-Barca, Bouke G. Hepkema, Constanze Schoenemann, Juergen May, Antonio Pezzutto, Hanno Riess

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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-B 18 (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.

    Original languageEnglish
    Pages (from-to)1093-1100
    Number of pages8
    JournalTransplantation
    Volume82
    Issue number8
    DOIs
    Publication statusPublished - 27-Oct-2006

    Keywords

    • human leukocyte antigen
    • solid organ transplantation
    • posttransplant lymphoproliferative disease
    • Epstein-Barr virus
    • FAMILIAL HODGKINS-DISEASE
    • CYTOTOXIC T-LYMPHOCYTES
    • KAPOSIS-SARCOMA
    • CLASS-I
    • NASOPHARYNGEAL CARCINOMA
    • NUCLEAR ANTIGEN-3
    • CYCLE PROTEINS
    • HLA ANTIGENS
    • VIRUS
    • CELLS

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