title: Determining donor-specific antibody C1q-binding ability improves the prediction of antibody-mediated rejection in human leucocyte antigen-incompatible kidney transplantation.
abstract: Detrimental impact of preformed donor-specific antibodies (DSAs) against human leucocyte antigens on outcomes after kidney transplantation are well documented, however, the value of their capacity to bind complement for predicting antibody-mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed to study DSA characteristics (strength and C1q binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen bead (SAB) assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with detectable anti-HLA antibodies). Patients were divided into DSA strength (MFI < vs. ≥ 15 000) and C1q-binding ability. AMR frequency was high (30%) and it increased with DSA strength (P = 0.002) and C1q+ DSA (P < 0.001). The performance of DSA C1q-binding ability as a predictor of AMR was better than DSA strength (diagnostic odds ratio 16.3 vs. 6.4, respectively). Furthermore, a multivariable logistic regression showed that C1q+ DSA was a risk factor for AMR (OR = 16.80, P = 0.001), while high MFI DSAs were not. Graft survival was lower in high MFI C1q+ DSA in comparison with patients with C1q- high or low MFI DSA (at 6 years, 38%, 83% and 80%, respectively; P = 0.001). Both DSA strength and C1q-binding ability assessment seem valuable for improving pretransplant risk assessment. Since DSA C1q-binding ability was a better predictor of AMR and correlated with graft survival, C1q-SAB may be a particularly useful tool.
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Malheiro
authors.affiliation: Centro do Sangue e Transplantação do Porto, Porto, Portugal.
authors.forename: Sandra
authors.identifier: http://orcid.org/0000-0002-3911-0245
authors.initials: S
authors.lastname: Tafulo
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Leonídio
authors.initials: L
authors.lastname: Dias
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: La Salete
authors.initials: S
authors.lastname: Martins
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fonseca
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Idalina
authors.initials: I
authors.lastname: Beirão
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Castro-Henriques
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Cabrita
mesh_terms: D000328:Adult; D000465:Algorithms; D001706:Biopsy; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007518:Isoantibodies; D015922:Complement C1q
keywords: C1q-binding antibodies; antibody-mediated rejection; donor-specific antibodies; kidney transplantation