title: Clinical significance of MHC-reactive alloantibodies that develop after kidney or kidney-pancreas transplantation.
abstract: The purpose of this study was to determine the relationships between acute rejection, anti-major histocompatibility complex (MHC) class I and/or class II-reactive alloantibody production, and chronic rejection of renal allografts following kidney or simultaneous kidney-pancreas transplantation. Sera from 277 recipients were obtained pretransplant and between 1 month and 9.5 years post-transplant (mean 2.6years). The presence of anti-MHC class I and class II alloantibodies was determined by flow cytometry using beads coated with purified MHC molecules. Eighteen percent of recipients had MHC-reactive alloantibodies detected only after transplantation by this method. The majority of these patients produced alloantibodies directed at MHC class II only (68%). The incidence of anti-MHC class II, but not anti-MHC class I, alloantibodies detected post-transplant increased as the number of previous acute rejection episodes increased (p = 0.03). Multivariate analysis demonstrated that detection of MHC class II-reactive, but not MHC class I-reactive, alloantibodies post-transplant was a significant risk factor for chronic allograft rejection, independent of acute allograft rejection. We conclude that post-transplant detectable MHC class II-reactive alloantibodies and previous acute rejection episodes are independent risk factors for chronic allograft rejection. Implementing new therapeutic strategies to curtail post-transplant alloantibody production, and avoidance of acute rejection episodes, may improve long-term graft survival by reducing the incidence of chronic allograft rejection.
authors.affiliation: Department of Surgery, The Ohio State University College of Medicine, Columbus 43210, USA. Pelletier-1@medctr.osu.edu
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Pelletier
authors.forename: Patrice K
authors.initials: PK
authors.lastname: Hennessy
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Adams
authors.forename: Anne M
authors.initials: AM
authors.lastname: VanBuskirk
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Ferguson
authors.forename: Charles G
authors.initials: CG
authors.lastname: Orosz
mesh_terms: D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D016035:Pancreas Transplantation / Q000276:immunology*; D011184:Postoperative Period; D044469:Racial Groups; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies