Background Sporadic inclusion body myositis (sIBM) is an intractable muscle disease that frequently affects elderly people. Autoantibodies recognising cytosolic 5’-nucleotidase 1A (cN1A) were found in the sera of patients with sIBM. However, the pathogenic role of the autoantibodies remained unknown. This study investigated the pathogenic properties of the autoantibodies using active cN1A peptides immunisation.
Methods Wild-type C57BL6 mice were injected with three different mouse cN1A peptides corresponding to the previously reported epitope sequences of human cN1A. After confirming the production of autoantibodies to the corresponding cN1A peptides in each group, changes in body weight, exercise capacity by treadmill test and histological changes in mice injected with cN1A peptides or controls were investigated.
Results Autoantibodies against cN1A were detected in serum samples from mice injected with cN1A peptide. Some groups of mice injected with cN1A peptide showed significant weight loss and decreased motor activity. The number of myofibres with internal nuclei increased in all the peptide-injected groups, with surrounding or invading CD8-positive T cells into myofibres, abnormal protein aggregates and overexpression of p62 and LC3.
Conclusions Active cN1A peptide immunisation partially reproduced the clinical and histological aspects of sIBM in wild-type mice. The murine model demonstrates the pathogenic properties of anti-cN1A autoantibodies to cause sIBM-like histological changes.
- INCL body myositis
Data availability statement
Data are available on reasonable request. All supporting data within the article are available on reasonable request from a qualified investigator.
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Contributors SY and NT contributed to the conception and design of the study. SY, KS, NS, IN and MA collected clinical data and patient samples for analysis. SY, NT, ZZ, SN, KS, NS, IN and MA contributed to the acquisition and analysis of data and designed and conducted experiments. SY, NT, ZZ, SN, KS, NS, IN and MA contributed to drafting the text and preparing the figures. SY is responsible for overall content as guarantor and accepts full responsibility for the finished work and the conduct of the study, had access to the data and controlled the decision to publish.
Funding This work was supported by a Grant-in-Aid for Scientific Research (20K07870) from the Japan Society for the Promotion of Science (JSPS), Japan; and a Grant-in-Aid for Research (20FC1006, 20FC1036, 23FC1014) on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.