P.12Active immunization mouse model of sporadic inclusion body myositis by cN1A peptides

Abstract

Sporadic inclusion body myositis (sIBM) is an intractable progressing inflammatory myopathy frequently affects elderly people. Lack of effective treatments and unclearness of pathogenesis in sIBM may be associated with absence of appropriate animal models. Recently, autoantibodies recognizing cytoplasmic 5′-nucleotidase 1a (cN1A) have been found in the sera of sIBM patients. However the roles of the anti-cN1A autoantibodies and autoreactive T cells are still unknown. In the current study, we aimed to generate the active immunization mouse model by cN1A peptides to realize the pathogenesis of sIBM. Three different sequences of murine cN1A peptides with complete Freund's adjuvant (CFA) were injected into the bilateral foot pads of C57BL/6J mice (n= 5 per each peptide). Pertusis toxins (PT) were injected intraperitoneally at the same time. Injection of peptides and CFA were repeated 3 times every week. As control mice, CFA and PT were injected alone. We evaluated time course of body weight, motor activity and myopathological changes. Autoantibodies recognizing injected cN1A peptides were detected in the sera of all the mice injected with cN1A peptides. Two of 3 peptide-injected groups showed significant decrease in motor activity. Inflammatory infiltrations of mononuclear cells including CD8-positive cells, surrounding or invading myofibers, were detected in the muscle specimens of the peptide-injected groups. Expression levels of p62 and LC3-II were increased in the muscle lysates from one of three peptide-injected group. Active immunization mouse model of cN1A peptides mimics histological and clinical aspects of sIBM. This murine model provides a useful tool for understanding the pathogenesis of sIBM and for developing new therapeutic strategies.