Identification and Long-Term Consequences of Antibodies Which Bound C1q in 118 Kidney Transplant Recipients With Donor Specific Antibodies.

Abstract

Introduction: Donor specific antibodies (DSA) play an important role in antibody-mediated rejection (ABMR) and graft dysfunction. Newer antibody detection assay Luminex® is highly sensitive but not accurately predictive of clinical outcomes. A more precise characterization of potentially harmful DSA is still a matter of concern. Patients and Methods: 118 recipients (8%) among 947 adult kidney transplant followed in Universitary Strasbourg Hospital had a functional graft and DSA in 2011. We identified DSA by Single Antigen Beads (SAB), and analyzed their potential to activate the complement by binding C1q using a Luminex® C1q assay (One Lambda). We correlate these results with the presence of ABMR, kidney biopsy morphological features, C4d staining and graft function. Results: Median follow up of sensitized patients was 8.5±6.5 years (3 months to 31 years). 65/118 patients (55%) were sensitized before transplantation. DSA identified by SAB were mainly class II (72%). 55 patients (47%) had antibodies that bound C1q (DSA C1q+). DSA C1q+ were de novo in 45 patients. Eighty of the 118 patients underwent one or several kidney allograft biopsies for cause (n=135). Mean delay between DSA apparition and kidney biopsy was 4.5±5.4 years.77 biopsies met criteria for ABMR, 29 with lesions of acute rejection and 48 with chronic lesions. 64% of patients with ABMR had DSA C1q+. 76% of patients who did not have ABMR had DSA C1q-. Microcirculation inflammation and chronic lesions were more pronounced in patients with DSA C1q+ than in patients with DSA C1q-, particularly when biopsies were done more than 5 years after DSA occurrence (cg score 1.98±1.3 vs. 0.55±1.1, p=0.0001). C4d staining was positive in 64% of patients with DSA C1q+ and negative in 64% of patients with DSA C1q-. Patients with DSA C1q+ had a poorer graft function (SCr 164 ± 75μmol/l) compared to those with DSA C1q- (SCr 146 ± 57μmol/l). Conclusion:DSA that bound C1q are mainly HLA class II and de novo DSA. Our data suggest that these DSA, as determined by the C1q assay, are associated with greater risk of ABMR, severe chronic tissue injury and allograft dysfunction.