title: The significance of donor-specific HLA antibodies in rejection and ductopenia development in ABO compatible liver transplantation.
abstract: The role of humoral alloreactivity in ABO-compatible liver transplantation remains unclear. To understand the significance of donor-specific HLA alloantibodies (DSA) in liver rejection, we applied the currently used strategy for detection of antibody-mediated rejection of other solid allografts. For this purpose we reviewed the data on 43 recipients of ABO identical/compatible donor livers who had indication liver biopsy stained for complement element C4d and contemporaneous circulating DSA determination. Seventeen (40%) patients had significant circulating DSA in association with diffuse portal C4d deposition (DSA+/diffuse C4d+). These DSA+/diffuse C4d+ subjects had higher frequency of acute cellular rejection (ACR) 15/17 versus 13/26 (88% vs. 50%), p = 0.02, and steroid resistant rejection 7/17 versus 5/26 (41% vs. 19%), p = 0.03. Based on detection of the combination DSA+/diffuse C4d+, 53.6% of cases of ACR had evidence of concurrent humoral alloreactivity. Six of the 10 patients with ductopenic rejection had circulating DSA and diffuse portal C4d, three of whom (2 early and 1 late posttransplantation) developed unrelenting cholestasis, necessitating specific antibody-depleting therapy to salvage the allografts. Thus, in ABO-compatible liver transplantation humoral alloreactivity mediated by antibodies against donor HLA molecules appears to be frequently intertwined with cellular mechanisms of rejection, and to play a role in ductopenia development.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. aim@medicine.wisc.edu
authors.forename: A I
authors.initials: AI
authors.lastname: Musat
authors.forename: R M
authors.initials: RM
authors.lastname: Agni
authors.forename: P Y
authors.initials: PY
authors.lastname: Wai
authors.forename: J D
authors.initials: JD
authors.lastname: Pirsch
authors.forename: D F
authors.initials: DF
authors.lastname: Lorentzen
authors.forename: A
authors.initials: A
authors.lastname: Powell
authors.forename: G E
authors.initials: GE
authors.lastname: Leverson
authors.forename: J M
authors.initials: JM
authors.lastname: Bellingham
authors.forename: L A
authors.initials: LA
authors.lastname: Fernandez
authors.forename: D P
authors.initials: DP
authors.lastname: Foley
authors.forename: J D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: A M
authors.initials: AM
authors.lastname: D'Alessandro
authors.forename: M R
authors.initials: MR
authors.lastname: Lucey
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001649:Bile Duct Diseases / Q000209:etiology* / Q000473:pathology; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012307:Risk Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d