Association of C1q-fixing DSA with late graft failure in pediatric renal transplant recipients.

Abstract

We investigated the prognostic value of overall and complement-binding donor-specific HLA antibodies (DSA) in pediatric patients undergoing clinically indicated graft biopsies and their association with graft outcome and specific histological lesions. Sera of 62 patients at time of indication biopsy ≥1year posttransplant were assessed for DSA and C1q-fixing DSA by single-antigen bead (SAB) technology. Twenty-six patients (42%) were DSA-positive at time of indication biopsy and nine (15%) were C1q-positive. At 4years postbiopsy, patients with C1q-positivity had a low graft survival (11%) compared to DSA-positive, C1q-negative patients (82%, p = 0.001) and to DSA-negative patients (88%, p < 0.001). The majority (89%) of C1q-positive patients were diagnosed with active chronic antibody-mediated rejection (ABMR). C1q DSA-positivity [adjusted hazard ratio (HR) 6.35], presence of transplant glomerulopathy (HR 9.54), and estimated glomerular filtration rate (eGFR) at the time of indication biopsy (HR 0.91) were risk factors for subsequent graft loss. The presence of C1q-positive DSA in the context of an indication biopsy identifies a subgroup of pediatric renal transplant recipients with a markedly increased risk of subsequent graft loss. Because a fraction of DSA-positive patients escape rejection or graft dysfunction, the C1q assay increases the specificity of a positive DSA result regarding unfavorable transplant outcome.