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

Transplantation. 2006 Oct 27;82(8):1093-100. doi: 10.1097/


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen Presentation
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Epitopes / chemistry
  • Female
  • HLA Antigens / chemistry*
  • HLA Antigens / immunology
  • Haplotypes
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Lymphoproliferative Disorders / immunology*
  • Male
  • Middle Aged
  • Organ Transplantation / methods*
  • Postoperative Complications
  • Retrospective Studies
  • Risk


  • Epitopes
  • HLA Antigens