Prognostic Value of the Persistence of C1q-Binding Anti-HLA Antibodies in Acute Antibody-Mediated Rejection in Kidney Transplantation

Background The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. Methods We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment. Results Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (p=0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (p=0.006), greater C4d score deposition score at 6 months after ABMR (p=0.008) and graft loss 5 years after ABMR (p=0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect. Conclusion The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification. Corresponding author: Elodie Bailly, Service de Néphrologie - Transplantation rénale, 2 boulevard Tonnellé, 37000 Tours, France, elodie.bailly@univ-tours.fr E.B., Y.L. and M.B. participated in the research design. E.B., D.A. and M.B. participated in the writing of the paper. E.B., D.A., G.B., P.G., V.V., V.C., E.M., P.M., A.P., J.T., G.G., J.S., C.M., P.G., I.T., M.L.Q., R.P., P.-F.W., B.P., V.C., Y.L., F.D. and M.B. participated in the performance of the research. E.B., B.P., V.C., Y.L. and M.B. participated in data analysis. B.P., F.D. and V.C. contributed analytic tools. The authors declare no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2idV8r6