title: Donor and recipient HLA/KIR genotypes do not predict liver transplantation outcome.
abstract: Whether or not Natural Killer (NK) cells affect the immune response to solid organ allografts is still controversial. Main determinants of NK-cell activation are specific HLA/killer-cell immunoglobulin-like receptors (KIR) interactions that, in transplantation, may induce NK-cell alloreactivity. So far, in liver transplantation (LTX) donor-versus-recipient alloreactivity has not been investigated; in addition, studies of predicted recipient-versus-donor NK-cell alloreactivity have led to contradicting results. We typed a cohort of LTX donors and recipients for HLA-C/Bw4 and KIRs. We estimated the effect of NK-cell alloreactivity, as predicted by classically used models, in the donor-versus-recipient direction. The results indicate that HLA/KIR mismatches in the donor-versus-recipient direction do not predict graft rejection nor graft or patient survival, suggesting that donor-derived NK cells do not play a major role in LTX outcome. In addition, when considering predicted NK-cell alloreactivity in the reverse direction (recipient-versus-donor), we first confirmed that donor HLA-C genotype was not associated with acute rejection, graft or patient survival and secondly we found that none of the models describing NK-cell alloreactivity could predict LTX outcome. Overall our observations suggest that, in contrast to what is shown in haematopoietic stem cell transplantation, donor-derived NK cells may not contribute in preventing liver graft rejection, and that recipient-versus-donor NK-cell alloreactivity does not predict LTX outcome.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Viviana
authors.initials: V
authors.lastname: Moroso
authors.forename: Arnold
authors.initials: A
authors.lastname: van der Meer
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Geert
authors.initials: G
authors.lastname: Kazemier
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D054340:Receptors, KIR