Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss

Authors


Scott Sutherland, MD, Division of Nephrology, Department of Pediatrics, Stanford University Medical Center, 300 Pasteur Drive, Room G-306, Stanford, CA 94305, USA
Tel.: 650 723 7903
Fax: 650 498 6714
E-mail: suthersm@stanford.edu

Abstract

Sutherland SM, Chen G, Sequeira FA, Lou CD, Alexander SR, Tyan DB. Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss.
Pediatr Transplantation 2012: 16: 12–17. © 2011 John Wiley & Sons A/S.

Abstract:  Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q(+) DSA]. Patients with C1q(+) DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q(+) DSA were nearly six times more likely to lose their transplant than those with C1q(−) DSA. Additionally, patients with C1q(+) DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss.

Ancillary