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Cruzipain induces autoimmune response against skeletal muscle and tissue damage in mice
L Giordanengo1, R Fretes, H Díaz
1Immunology Unit, Department of Clinical Biochemistry, College of Chemical Sciences, National University of Córdoba, Argentina.
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.
Insights
This study shows that the Trypanosoma cruzi antigen, cruzipain, can trigger an autoimmune response in mice, leading to skeletal muscle damage. This research highlights a potential mechanism for muscle injury in Chagas disease.
Area of Science:
- Immunology
- Parasitology
- Neurology
Background:
- Cruzipain is a major antigen of Trypanosoma cruzi, the parasite causing Chagas disease.
- Autoimmune responses can lead to tissue damage, including skeletal muscle pathology.
Purpose of the Study:
- To investigate if cruzipain induces autoimmune responses and skeletal muscle damage in a mouse model.
- To explore the pathogenic role of anti-cruzipain immunity in muscle tissue injury.
Main Methods:
- Immunization of mice with purified cruzipain.
- Detection of specific antibodies (immunoglobulin G) against skeletal muscle antigens.
- Spleen cell proliferation assays using skeletal muscle extracts and purified myosin.
- Biochemical analysis of plasma creatine kinase activity.
- Histological examination of skeletal muscle tissue.
- Electromyographic studies to assess muscle function.
Main Results:
- Immunization with cruzipain led to the production of antibodies that bind to myosin, a skeletal muscle protein.
- Spleen cells from immunized mice showed proliferation in response to myosin.
- Increased plasma creatine kinase activity indicated muscle damage.
- Histological analysis revealed inflammatory infiltrates and myopathic changes in skeletal muscle.
- Electromyography showed changes consistent with inflammatory or necrotic myopathy.
Conclusions:
- The anti-cruzipain immune response in mice is associated with the development of skeletal muscle damage.
- This experimental model provides evidence for a pathogenic role of cruzipain in muscle tissue injury.
- The findings suggest a potential mechanism for muscle pathology in Chagas disease related to autoimmune responses against self-antigens like myosin.