The clinical utility of preformed C1q-binding donor-specific HLA antibodies in kidney transplantation
Sua Lee1,2,4, Eun Jeong Ko1,2, Byung Ha Chung1,2,3, Chul Woo Yang1,2,3.
1Transplant Research center, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; 2Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; 3Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; 4Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Background: The anti-human leukocyte antigen (HLA) antibodies are well known for risk factor of rejection or allograft loss in kidney transplantation (KT). Additionally, de novo complement component 1q-binding donor-specific anti-HLA antibodies (C1q-binding DSAs) are already reported to be associated with an increased risk of acute allograft rejection in KT. Recently, the clinical impact of preformed C1q-binding DSAs has been discussed. This study investigated the clinical utility of identification of preformed C1q-binding DSAs for predicting graft outcomes in KT.
Methods: From December 2016 to December 2018, 323 recipients underwent KT at Seoul St. Mary's Hospital. If the results of panel reactive antibodies (PRA) were positive in the pre-transplant examination, DSAs and C1q-binding DSAs were performed using Luminex Single Antigen Bead Assay (SAB) at the same time. Graft outcomes in term as Chronic Kidney Disease-Epidemiology Collaboration estimated Glomerular Filtration Rate (CKD-EPI eGFR), acute rejection and graft survival were compared between recipients with preformed C1q-binding DSAs and recipients without preformed C1q-binding DSAs.
Results: Eighty-two of 323 recipients (25.4%) were evaluated DSAs and C1q-binding DSAs before transplantation. Among them, 40 recipients (48.8%) had preformed DSAs and 8 recipients (9.9%) had preformed C1q-binding DSAs. There were no significant difference in basic demographics except for administration of bortezomib for desensitization between C1q-binding DSAs(-) group and C1q-binding DSAs(+) group. The higher MFI values of DSAs had the higher rate of prevalence of C1q-binding DSAs (9263.9 ± 3670.3 vs. 5955.3 ± 5245.5; p = 0.050). Especially, there was a strong correlation between the presence of DSAs against Class II and C1q-binding DSAs (p = 0.007; CI 95%, OR 9.333). Five of 21 patients (23.8%) with positive at least one of complement-dependent cytotoxicity (CDC) or flow cytometry crossmatch (FCXM) had preformed C1q-binding DSAs. There was a correlation between positivity of crossmatch and preformed C1q-binding DSAs (p = 0.024;CI 95%, OR 6.042). Four of 8 recipients (50%) in C1q-binding DSAs(+) group were confirmed acute antibody-mediated rejection by allograft biopsy. This result showed that C1q-binding DSAs(+) group had significantly higher incidence of acute antibody mediated rejection than that of C1q-binding DSAs(-) group (p=0.044; CI 95%, OR 4.286).
Conclusion: The identification of preformed C1q-binding DSAs may be important in predicting acute antibody-mediated rejection in KT. Therefore, the surveillance such as protocol allograft biopsy is required for early detection of acute antibody-mediated rejection after transplantation for patients with preformed C1q-binding DSAs.
