title: De novo donor-specific HLA antibodies decrease patient and graft survival in liver transplant recipients.
abstract: The role of de novo donor-specific HLA antibodies (DSA) in liver transplantation remains unknown as most of the previous studies have only focused on preformed HLA antibodies. To understand the significance of de novo DSA, we designed a retrospective cohort study of 749 adult liver transplant recipients with pre- and posttransplant serum samples that were analyzed for DSA. We found that 8.1% of patients developed de novo DSA 1 year after transplant; almost all de novo DSAs were against HLA class II antigens, and the majority were against DQ antigens. In multivariable modeling, the use of cyclosporine (as opposed to tacrolimus) and low calcineurin inhibitor levels increased the risk of de novo DSA formation, while a calculated MELD score >15 at transplant and recipient age >60 years old reduced the risk. Multivariable analysis also demonstrated that patients with de novo DSA at 1-year had significantly lower patient and graft survival. In conclusion, we demonstrate that de novo DSA development after liver transplantation is an independent risk factor for patient death and graft loss.
authors.affiliation: University of California, Los Angeles, Los Angeles, CA, USA. hkaneku@mednet.ucla.edu
authors.forename: H
authors.initials: H
authors.lastname: Kaneku
authors.forename: J G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: N
authors.initials: N
authors.lastname: Banuelos
authors.forename: L W
authors.initials: LW
authors.lastname: Jennings
authors.forename: B M
authors.initials: BM
authors.lastname: Susskind
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006680:HLA Antigens