Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation

Background: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. Methods: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. Results: dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. Conclusions: Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.

Automated summary

This study evaluated the association between complement-fixing dnDSA antibodies and graft loss, as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. The presence of C1q-binding dnDSA was significantly associated with rejection frequency and renal graft loss. These findings suggest that classifying dnDSA based on their ability to activate the complement and detecting complement-binding capacity could serve as prognostic markers for predicting AMR outcome and graft survival in kidney transplant patients who develop dnDSA.