Clinical Outcome of Patients With De Novo C1q-Binding Donor-Specific HLA Antibodies After Renal Transplantation

Background De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent and harmful dnDSA causing antibody-mediated rejection (AMR) and graft loss. Methods We retrospectively identified 59 renal transplant recipients who developed dnDSA and had serum available and complete follow-up. All patients were analyzed for C1q-binding dnDSA at the time of dnDSA detection, and 1-year later or at time of AMR. AMR-positive patients were also tested 6 to 12 months before the event if IgG dnDSA was present. Results Thirty-seven of 59 dnDSA(+) patients developed AMR during 5.9 3.1 years follow-up. AMR-positive patients had more dnDSA with a significant higher frequency of class I, a higher frequency and a higher mean fluorescence intensity value of C1q(+)-dnDSA at all time-points. Death-censored AMR-free and allograft survivals were significantly lower in C1q(+)-dnDSA patients. In multivariate analysis, C1q(+)-dnDSA was an independent risk factor for AMR. Conclusions C1q-binding dnDSA is associated with inferior outcomes, yet not in all patients. Nevertheless, C1q(+)-dnDSA was shown to be an independent risk factor of AMR and graft loss and may be a useful tool to stratify the immunological risk for AMR.