title: Solid phase detection of C4d-fixing HLA antibodies to predict rejection in high immunological risk kidney transplant recipients.
abstract: Protocols for recipient desensitization may allow for successful kidney transplantation across major immunological barriers. Desensitized recipients, however, still face a considerable risk of antibody-mediated rejection (AMR), which underscores the need for risk stratification tools to individually tailor treatment. Here, we investigated whether solid phase detection of complement-fixing donor-specific antibodies (DSA) has the potential to improve AMR prediction in high-risk transplants. The study included 68 sensitized recipients of deceased donor kidney allografts who underwent peritransplant immunoadsorption for alloantibody depletion (median cytotoxic panel reactivity: 73%; crossmatch conversion: n = 21). Pre and post-transplant sera were subjected to detection of DSA-triggered C4d deposition ([C4d]DSA) applying single-antigen bead (SAB) technology. While standard crossmatch and [IgG]SAB testing failed to predict outcomes in our desensitized patients, detection of preformed [C4d]DSA (n = 44) was tightly associated with C4d-positive AMR [36% vs. 8%, P = 0.01; binary logistic regression: odds ratio: 10.1 (95% confidence interval: 1.6-64.2), P = 0.01]. Moreover, long-term death-censored graft survival tended to be worse among [C4d]DSA-positive recipients (P = 0.07). There were no associations with C4d-negative AMR or cellular rejection. [C4d]DSA detected 6 months post-transplantation were not related to clinical outcomes. Our data suggest that pretransplant SAB-based detection of complement-fixing DSA may be a valuable tool for risk stratification.
authors.affiliation: Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bartel
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwaiger
authors.forename: Željko
authors.initials: Ž
authors.lastname: Kikić
authors.forename: Christine
authors.initials: C
authors.lastname: Winzer
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mühlbacher
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoke
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000327:Adsorption; D000328:Adult; D000906:Antibodies / Q000302:isolation & purification*; D015331:Cohort Studies; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000378:metabolism*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D007518:Isoantibodies / Q000302:isolation & purification; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d