Cruzipain induces autoimmune response against skeletal muscle and tissue damage in mice

Abstract

The goal of the current study was to investigate whether cruzipain, a major Trypanosoma cruzi antigen, is able to induce in mice an autoimmune response and skeletal muscle damage. We demonstrate that immunization with cruzipain triggers immunoglobulin G antibody binding to a 210‐kDa antigen from a syngeneic skeletal muscle extract. The absorption of immune sera with purified myosin completely eliminated this reactivity, confirming that the protein identified is really myosin. We also found that spleen cells from immunized mice proliferated in response to a skeletal muscle extract rich in myosin and to purified myosin. Cells from control mice did not proliferate against any of the antigens tested. In addition, we observed an increase in plasma creatine kinase activity, a biochemical marker of muscle damage. Histological studies showed inflammatory infiltrates and myopathic changes in skeletal muscle of immunized animals. Electromyographic studies of these mice revealed changes such as are found in inflammatory or necrotic myopathy. Altogether, our results suggest that this experimental model provides strong evidence for a pathogenic role of anticruzipain immune response in the development of muscle tissue damage. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 1407–1413, 2000.

Myosin Autoimmunity Is Not Essential for Cardiac Inflammation in Acute Chagas’ Disease

“…The simplest explanation for this observation is that there is immunologic crossreactivity between a host Ag, such as myosin, and an immunodominant T. cruzi Ag (manuscript in preparation) (8,(42)(43)(44)(45). This could possibly be the myosin-B13 cross-reactive epitope described by Cunha-Neto et al (8,46), although this awaits further study.…”

Advances in Serological Diagnosis of Chagas' Disease by Using Recombinant Proteins

“…(Leon & Engman, 2001) Among these antigens we should mention cruzipain, (Giordanengo et al, 2000;Goin et al, 1999;Duschak et al, 2001) sulfo-cerebrosides (Avila et al, 1993) and the ribosomal protein TcP2. (Levitus et al, 1991) Precursor works had described that this ribosomal antigen that shares the C terminal region with its homologous from humans, generated autoimmune antibodies, whose concentration was increased in patients who had developed chagasic cardiopathy.…”

The Contribution of Autoimmunity to Chagas Heart Disease

“…Specifically, immunization of mice with regions of the T. cruzi ribosomal P1 and P2 protein induced production of autoantibodies to the mouse ribosomal proteins as well as electrocardiographic alterations (Motran et al, 2000). Immunization with cruzipain induced autoantibodies and T cell responses to myosin, skeletal myositis (Giordanengo et al, 2000a), and cardiac conduction abnormalities (Giordanengo et al, 2000b). Since no live parasites were used, the autoimmunity is believed to be induced through a molecular mimicry mechanism.…”

“…When a parasite antigen closely resembles a host antigen, the immune system may be induced first against the parasite antigen and then "cross-react" with a self antigen, causing autoimmunity. Evidence for this hypothesis includes the reports of autoimmunity upon immunization with a T. cruzi antigen (Giordanengo et al, 2000a;Motran et al, 2000) and the many reports of cross-reactive (T. cruzi-host) autoantibodies such as B13-myosin (Cunha-Neto et al, 1995), or cruzipain-myosin (Giordanengo et al, 2000b), T. cruzi-mammalian ribosomal P proteins (Motran et al, 2000) and T. cruzi shed acute phase antigen-Cha autoantigen (Girones et al, 2001). …”