Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation.
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.
Subklewe
Marion
M
Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Med. Klinik m. S. Haematologie/Onkologie, Berlin, Germany. marion.subklewe@charite.de
Marquis
René
R
Choquet
Sylvain
S
Leblond
Veronique
V
Garnier
Jeanne-Luce
JL
Hetzer
Roland
R
Swinnen
Lode J
LJ
Oertel
Stephan
S
Papp-Vary
Matthias
M
Gonzalez-Barca
Eva
E
Hepkema
Bouke G
BG
Schoenemann
Constanze
C
May
Juergen
J
Pezzutto
Antonio
A
Riess
Hanno
H
D000328:Adult; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006680:HLA Antigens / Q000737:chemistry* / Q000276:immunology; D006239:Haplotypes; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000379:methods*; D011183:Postoperative Complications; D012189:Retrospective Studies; D012306:Risk
D000939:Epitopes; D006680:HLA Antigens