Association Between De Novo C1q-Binding Donor-Specific Anti-HLA Antibodies and Clinical Outcomes After Kidney Transplantation: A Meta-Analysis

Background: Donor-specific antibodies (DSAs) are recognized as an important factor of kidney allograft loss as a subsequent event of antibody-mediated rejection (AMR). The clinical relevance of de novo DSAs (dnDSAs) after kidney transplant, particularly in their ability to bind C1q, has been widely investigated to various extents among studies. A recent study was performed to examine the association between C1q-binding dnDSAs and succeeding clinical events after kidney transplant. Methods: A meta-analysis of studies published before April 2021 was conducted from PubMed, Science Direct, and Cochrane databases. Publications on dnDSA after kidney transplant focusing on differentiation between C1q-binding and non–C1q-binding were included. The outcomes analyzed were AMR rate and allograft loss. Studies using preformed DSA were excluded. The pooled risk ratio and 95% confidence interval (CI) were analyzed using Mantzel-Haenzel method, and the I² value was used to determine the heterogeneity of the studies. Data analysis was conducted using Review Manager 5.3. Results: A total of 535 patients from 13 studies who developed dnDSA after kidney transplant were analyzed. Among these, 239 (44.7%) had C1q-binding and 296 (55.3%) had non–C1q-binding dnDSA. Acute AMR was found in 59.2% (97/164) of the C1q-binding group and in 28.8% (49/170) of the non–C1q-binding group (risk ratio [RR], 0.58 [95% CI, 0.39-0.85], P = .006, I² = 58%). Chronic AMR was found in 50% (19/38) of the C1q-binding group and in 16.9% (11/65) of the non–C1q-binding group (RR, 0.39 [95% CI, 0.21-0.71], P = .002, I² = 0%). Allograft loss was found in 62.2% (74/119) of the C1q-binding group and in 34.1% (60/176) of the non–C1q-binding group (RR, 0.57 [95% CI, 0.38-0.85], P = .006, I² = 61%). Conclusions: This meta-analysis demonstrates that patients who developed C1q-binding dnDSA display an increased risk of AMR and allograft loss compared with those with non–C1q-binding dnDSA. Therefore, C1q-binding dnDSAs are associated with inferior outcomes after kidney transplant.