C1q-Fixing De Novo Donor Specific Antibodies in Therapeutic Management of Chronic Antibody-Mediated Rejection Postkidney Transplantation

Abstract

Evidence for C1q-fixing donor-specific antibodies (DSA) after chronic antibody-mediated rejection (CABMR) treatment is lacking. We investigated if C1q-DSA could predict therapy response in patients with biopsy-proven CABMR. Twenty kidney transplant patients with late-onset DSA were enrolled. Patients with biopsy-proven CABMR received three plasma pheresis sessions, one dose of rituximab (375 mg/m2), and steroid pulse therapy. We monitored IgG-DSA, C1q-DSA, and renal graft function for >2 years post-CABMR treatment. Patients with C1q-DSA mean fluorescence intensity (MFI) decreased by less than 50% post-treatment were classified as C1q-nonresponders. We compared Banff classification scores (g, ptc, cg, c4d) before and 6 months after treatment. Fourteen (70%) of 20 patients were C1q-DSA positive. The MFIs of IgG-DSA and C1q-DSA before treatment were significantly higher in the C1q-DSA positive group than in the negative group, at 20,035 and 10,918 (P = .008) and 17,702 and 21 (P < .001), respectively. Fifteen patients (75%) were diagnosed with CABMR via biopsy, and 12 patients received rejection therapy. Five (41.7%) patients were C1q-responders and seven (58.3%) were C1q-nonresponders. The MFIs of C1q-DSA before treatment were not significantly different between the two groups (11,521 vs. 13,985). Renal graft function was stable after treatment in C1q-responders for 3 years. In contrast, renal graft function tended to deteriorate in C1q-nonresponders. Biopsy showed improvement in scores in 75% of C1q-responders while deterioration in scores in 42.9% of C1q-nonresponders. C1q-DSA may be a good predictor of outcomes after CABMR treatment.