title: Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver.
abstract: Despite improvement in early outcome, rejection particularly chronic allograft enteropathy continues to be a major barrier to long-term visceral engraftment. The potential role of donor specific antibodies (DSA) was examined in 194 primary adult recipients. All underwent complement-dependent lymphocytotoxic crossmatch (CDC-XM) with pre- and posttransplant solid phase HLA-DSA assay in 156 (80%). Grafts were ABO-identical with random HLA-match. Liver was included in 71 (37%) allografts. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 150 (77%). CDC-XM was positive in 55 (28%). HLA-DSA was detectable before transplant in 49 (31%) recipients with 19 continuing to have circulating antibodies. Another 19 (18%) developed de novo DSA. Ninety percent of patients with preformed DSA harbored HLA Class-I whereas 74% of recipients with de novo antibodies had Class-II. Gender, age, ABO blood-type, cold ischemia, splenectomy and allograft type were significant DSA predictors. Preformed DSA significantly (p < 0.05) increased risk of acute rejection. Persistent and de novo HLA-DSA significantly (p < 0.001) increased risk of chronic rejection and associated graft loss. Inclusion of the liver was a significant predictor of better outcome (p = 0.004, HR = 0.347) with significant clearance of preformed antibodies (p = 0.04, OR = 56) and lower induction of de novo DSA (p = 0.07, OR = 24). Innovative multifaceted anti-DSA strategies are required to further improve long-term survival particularly of liver-free allografts.
authors.affiliation: Department of Surgery Department of Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. abuelmagdkm@upmc.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Abu-Elmagd
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Costa
authors.forename: J
authors.initials: J
authors.lastname: Lunz
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: D A
authors.initials: DA
authors.lastname: Koritsky
authors.forename: N
authors.initials: N
authors.lastname: Murase
authors.forename: W
authors.initials: W
authors.lastname: Irish
authors.forename: A
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001707:Biopsy, Needle; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000637:transplantation*; D007518:Isoantibodies / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies