title: Clinical relevance of preformed C4d-fixing and non-C4d-fixing HLA single antigen reactivity in renal allograft recipients.
abstract: Donor-specific alloantibodies (DSA), especially those fixing complement, may pose a particular immunologic risk to transplant recipients. To assess the clinical impact of C4d- or non-C4d-fixing (IgG) HLA sensitization, pretransplant sera obtained from 338 kidney allograft recipients prescreened by FlowPRA were retrospectively evaluated by Luminex single antigen (SA) testing using a novel fluorescent-labeled anti-C4d reagent for detection of antibody-triggered C4d deposition in addition to IgG binding. Recipients with [IgG]DSA (n = 39) showed a substantially higher rate of C4d positive rejection (33%) than 16 patients with [IgG] non-DSA (0%) or 283 antibody-negative patients (4%, multivariate analysis excluding retransplantation because of high co-linearity: P < 0.0001), and adversely affected 5-year death-censored graft survival (74% vs. 81% and 90%, respectively, multivariate model: P < 0.05). [C4d] DSA (n = 21) and [C4d] non-DSA (n = 25) increased rates of C4d positive rejections to a similar extent (24% and 28% vs. 4% in recipients without C4d-fixing reactivity; multivariate analysis: P <or= 0.002) with a trend towards adverse 5-year graft survival (76% and 76% vs. 90%; P <or= 0.2). In conclusion, Luminex-based characterization of HLA sensitization may be a useful strategy for risk stratification. Possibly as a result of intensified immunosuppression in presensitized recipients, identification of C4d-fixing DSA was not associated with a further increase of rejection and graft loss rates.
authors.affiliation: Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Gregor
authors.initials: G
authors.lastname: Bartel
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Günther F
authors.initials: GF
authors.lastname: Körmöczi
authors.forename: Gottfried F
authors.initials: GF
authors.lastname: Fischer
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D000937:Antigen-Antibody Reactions; D015935:Complement C4b / Q000276:immunology*; D003168:Complement Fixation Tests / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d