Background. Anti-HLA DQ antibodies are the predominant HLA class II donor-specific- antibodies (DSAs) after transplantation. Recently, de novo DQ DSA has been associated with worse allograft outcomes. The aim of this study was to determine the further complement-binding characteristics of the most harmful DQ DSA.

Methods. Single antigen beads (SAB) technology was used to screen 284 primary kidney transplant recipients for the presence of post-transplant DQ DSA. Peak DSA sera of 34 recipients with only de novo DQ DSA and of 20 recipients with de novo DQ plus other DSA were further analyzed by a modified SAB assay using IgG subclass-specific reporter antibodies and a C1q-binding assay.

Results. Compared with recipients who did not have DSA, those with de novo persistent DQ-only DSA and with de novo DQ plus other DSA had more acute rejection (AR) episodes (22%, p=0.005 and 36%, p=0.0009), increased risk of allograft loss (HR: 3.7, p=0.03 and HR: 11.4, p=0.001), and lower 5-year allograft survival [Fig1]. De novo DQ-only recipients with AR had more IgG1+IgG3 combination and C1q-binding antibodies (51%, p=0.01 and 63%, p=0.001, respectively) than patients with no AR. Furthermore, the presence of C1q-binding de novo DQ DSA was associated with 30% lower 5-year allograft survival (p=0.003) [Fig2].

Conclusion. The presence of de novo persistent, complement-binding IgG, DQ DSA negatively impacts kidney allograft outcomes. Therefore, early post-transplant detection, monitoring and removal of complement-binding DQ might be crucial for improving long-term kidney transplant outcomes.

Ozawa, M.: Employee, One Lambda, Inc. Nguyen, A.: Employee, One Lambda, Inc. Everly, M.: Employee, One Lambda, Inc. Sasaki, N.: Employee, One Lambda, Inc. Terasaki, P.: Stockholder, One Lambda, Inc.

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