Cruzipain Induces Autoimmune Response Against Skeletal Muscle and Tissue Damage in Mice

Muscle Nerve. 2000 Sep;23(9):1407-13. doi: 10.1002/1097-4598(200009)23:9<1407::aid-mus12>3.0.co;2-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmunity / drug effects*
  • Creatine Kinase / blood
  • Cysteine Endopeptidases / pharmacology*
  • Electromyography
  • Female
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / pathology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / immunology*
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology
  • Myosins / immunology
  • Myosins / metabolism
  • Protozoan Proteins
  • Spleen / immunology
  • Spleen / pathology

Substances

  • Autoantibodies
  • Autoantigens
  • Protozoan Proteins
  • Creatine Kinase
  • Cysteine Endopeptidases
  • cruzipain
  • Myosins