The Autoimmune Response to Vimentin After Renal Transplantation in Nonhuman Primates Is Immunosuppression Dependent

Abstract

We postulate that vimentin acts as an autoantigen after renal transplantation; it elicits an autoimmune response that is not regulated by cyclosporine. This autoimmune response may be part of the complex immunologic events occurring posttransplantation and may contribute to the development of CAN, but cannot be considered as a major cause of CAN because this condition also develops without antivimentin antibodies.

Expression Patterns of Regulatory T-Cell Markers in Accepted and Rejected Nonhuman Primate Kidney Allografts

“…The biopsies and the necropsy materials were scored for rejection according to the Banff '97 criteria (16). Results of these studies have been reported previously (9)(10)(11)15,(17)(18)(19)(20). Biopsies were divided into groups according to the presence or absence of rejection and subsequently according to the type of rejection.…”

Humoral Immunity to Vimentin Is Associated with Cardiac Allograft Injury in Nonhuman Primates

“…21 were given IDEC-131 (Biogen Idec, San Diego, CA) (12) using high (30 mg/kg at transplant, 15 mg/kg weekly × 2, then 20 mg/kg monthly; n = 10) or intensive (high regimen plus an additional 30 mg/kg on day 3, 20 mg/kg weekly × 2-3, and 30 mg/kg monthly as single or bi-weekly doses; n = 11) dosing strategies as described in detail elsewhere (AA manuscript submitted). Seven animals received a high-dose regimen of another anti-CD154 monoclonal, hu5c8 (15)(16)(17)(18)(19)(20) mg/kg at transplant and 5-10 mg/kg weekly, thereafter, for two additional doses; three then received 15-20 mg/kg monthly), as previously reported (13).…”

Autoantibodies to Vimentin Cause Accelerated Rejection of Cardiac Allografts

“…29 Nonhuman primates with renal allograft also make anti-vimentin antibodies (AVA), but the response is not significantly associated with development of renal graft vasculopathy. 30 This is the first study to design experiments to discover whether the autoimmune response to vimentin, and in particular anti-vimentin antibodies, actively contributes to graft rejection. The first part of the study investigated whether it was possible to break self-tolerance to vimentin in mice and, the second part, whether the autoimmune response to vimentin contributed to the pathogenesis of cardiac allograft rejection.…”