97 Autoimmunity to Cardiac Myosin Is Associated with Acute and Chronic Rejection of Cardiac Allografts in Non-Human Primates

Abstract

Purpose Immune responses to autoantigens have been described in animal and human allograft recipients. We previously reported immunity to vimentin with development of cardiac allograft vasculopathy (CAV) in non-human primates. Here we report immunity to cardiac myosin, a heart-specific autoantigen, after transplantation in this model. Methods and Materials Cynomolgus monkeys received a heterotopic heart allograft and were separated into 3 groups based on graft outcome: 1) Acute rejection (AR, median survival time [MST] 90 days), observed with CsA+anti-CD20. Antibodies (IgM and IgG) against human and monkey CM were assayed by ELISA until the time of graft explant. Positive samples were assayed for αCM IgG by western-blot. Results AR was associated with increased αCM IgM (9/15) and/or IgG (7/15) levels, detected within 30 days post transplantation. CsA was associated with moderate to severe CAV (CAV score >2); CM Abs were detected in 83% (5/6). When AR and CAV were prevented with CsA+B-cell depletion (CAV score Conclusions Detection of humoral immunity to cardiac myosin is closely associated with both acute and chronic rejection of cardiac allografts, but is not detected when CAV is prevented. We conclude that increasing titer of antibody against CM is a biologic marker for chronic cardiac allograft injury. Whether loss of immunoregulation (tolerance) to the autologous CM protein is an epiphenomenon or pathogenic remains to be determined. If immunity against CM contributes significantly to allograft injury, inducing robust tolerance to CM may help attenuate heart allograft injury.