Session Name: Kidney Acute Antibody Mediated Rejection
Session Date & Time: None. Available on demand.
*Purpose: Complement activation is one dominant mechanism which cause allograft injury in kidney transplantation (KT). Anti-HLA donor-specific antibodies (DSA) that bind to HLA molecules on graft endothelium are cross-linked by the C1 complex, which initiates the classical complement pathway. De novo complement component 1q-binding donor-specific anti-HLA antibodies (C1q-binding DSAs) are already reported as risk factor associated with acute allograft rejection in KT. This study investigated the clinical significance of preformed C1q-binding DSA for predicting graft outcomes in KT.
*Methods: From December 2016 to December 2018, 373 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. Mean fluorescence intensity above 1000 was defined as positive result. Patients with preformed anti-HLA DSA were classified as C1q-positive group and C1q-negative group. Acute rejection was defined as biopsy-proven rejection based upon the Banff classification. Primary outcome was acute antibody-mediated rejection (AMR).
*Results: Seventy five of 373 recipients (20.1 %) had preformed anti-HLA DSA, and of them, sixteen recipients (4.3 %) had preformed C1q-binding DSA. C1q-positive group had more positive PRA Class II and DSA class II (p = 0.036 and 0.050, respectively). And, DSA Class II MFI in C1q-positive group was significantly higher than in C1q-negative group (13796 (10746.5, 22883.5) vs. 3055.5 (1247.3, 7697.8); p < 0.001). In allograft outcomes according to the presence of C1q-binding DSA, the incidence of acute rejection in C1q-positive group is significantly higher than in C1q-negative group, especially acute AMR (p = 0.037 and 0.040, respectively). There was no significant difference in death-censored graft loss rate. In univariate logistic regression analysis, the presence of DSA Class II, 5000 or more of DSA MFI, the presence of C1q-binding DSA and C1q-binding DSA Class II were risk factors associated with acute ABR. However, in multivariate analysis, 5000 or more of DSA MFI was the only risk factor associated with acute AMR. In Kaplan-Meier analysis for the cumulative incidence of acute AMR, the incidence of acute AMR in C1q-binding DSA positive group was significantly higher than in C1q-binding DSA negative group (p = 0.012).
*Conclusions: Preformed C1q-binding DSA may be a risk factor associated with acute AMR. Surveillance, such as protocol allograft biopsy, can help to detect acute AMR early in recipients with preformed C1q-binding DSA.
To cite this abstract in AMA style:Lee S, Yang C, Chung B. The Clinical Significance of Preformed C1q-binding Donor-specific HLA Antibodies in Kidney Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/the-clinical-significance-of-preformed-c1q-binding-donor-specific-hla-antibodies-in-kidney-transplantation/. Accessed June 12, 2021.
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