Effect of C1q-binding donor-specific anti-HLA antibodies on the clinical outcomes of patients after renal transplantation: A systematic review and meta-analysis

Background: Complement-binding donor-specific human leukocyte antigen (HLA) antibodies in kidney recipients have been associated with a higher risk of allograft rejection and loss. The objective of this meta-analysis was to investigate the correlation between C1q-binding donor-specific antibodies (DSAs) and clinical outcomes in kidney transplantation (KT) recipients. Methods: We conducted systematic searches in the PubMed, EMBASE, and the Cochrane Library databases to identify all studies since inception to August 2021 that compared clinical outcomes between C1q + DSA and C1qDSA patients who underwent KT. Data were independently extracted by two reviewers who assessed the risk of bias. Data were summarized with fixed effects or random effects models according to heterogeneity. We assessed clinical outcomes including graft loss, rejection, delayed graft function (DGF), and all-cause patient death. Results: Twenty-six studies with a total of 1337 patients were included: 485 with C1q-binding DSAs, and 850 without C1q-binding DSAs. Compared with the C1q-DSA group, the C1q + DSA group had significant increases in antibody-mediated rejection (AMR) (relative risk [RR] = 2.09, 95% confidence interval [CI], 1.53-2.86; P < 0.00001), graft loss (RR = 2.40, 95% CI, 1.66-3.47; P < 0.00001), and death (RR = 3.13, 95% CI, 1.06-9.23; P = 0.04). The C1q + DSA and C1q-DSA groups did not show significant differences in T-cell-mediated rejection, acute rejection, acute cellular rejection, mixed rejection, or DGF. Conclusion: The findings of this systematic review suggest that C1q + DSA KT have a higher risk of AMR, graft loss, and death compared with C1q-DSA patients. Monitoring C1q-binding DSAs allows risk stratification of recipients and guides physician management.