P319 Histopathological features and autophagy aspects of Ku+ myositis

• Published in: Neuromuscular disorders : NMD Vol. 33; p. S94
• Main Authors: Preusse, C., Holzer, M., Schneider, U., Schänzer, A., Léonard-Louis, S., Benveniste, O., Weis, J., Claeys, K., Schoser, B., Montagnese, F., Uruha, A., Huber, M., Gallay, L., Streichenberger, N., Mrusche, K., Stenzel, W.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023
• DOI: 10.1016/j.nmd.2023.07.117
• ISSN: 0960-8966

Ku+ myositis is one of the rarer forms of myositis, with antibodies that are associated with many forms of connective tissue disease and the clinical picture of the patients often varies. A few histopathological examinations have shown a broad picture with inflammatory or necrotizing aspects, but a precise description and characterization of Ku+ myositis is still lacking. Therefore, the aim of this study was to perform a detailed histopathological and transcriptional examination of muscle samples from Ku+ patients with myositis to uncover possible pathophysiological mechanisms/commonalities. Muscle biopsies from 23 patients with positive Ku antibody status and clinical and morphological signs of myositis were analyzed histopathologically, immunohistochemically, and by quantitative PCR. Furthermore, a comparison was made with biopsies from non-disease controls (NDCs) and from patients with immune-mediated necrotizing myopathy (IMNM). We found that 91% of patients were women with an average age of 55 years. There was an overlap with systemic sclerosis in 30% of the cases and isolated myositis in 26%. Furthermore, overlap syndromes with primary Sjögren's syndrome (in 13% of cases) and with rheumatoid arthritis (also 13%) were present. All patients presented with myalgia, of which nine patients showed no clinical signs of muscle weakness. CK elevation was present in 91% of cases. Histopathological examinations showed a wide spectrum with mild to very pronounced myositis. MHC-cl. I showed greater overexpression than MHC-cl. II with diffuse, focally enhanced expression in each case. In almost all samples (87%), we noted varying degrees of necrosis with concurrent inflammatory aspects. We also noted small vacuoles in 59% of biopsies and p62+ and LC3+ and myotilin aggregates in 62%, 60%, and 76%, respectively. Immunofluorescence showed co-localization of p62 and myotilin. In this study, we identified a histopathological pattern of Ku+ myositis with predominant MHC-cl. I overexpression, inflammation, necrosis, and small vacuoles, as well as specific p62+, LC3+ aggregation especially in markedly inflammatory biopsies. Co-localization of p62 and myotilin may indicate protein aggregation and induction of autophagy pathways and is now the subject of continued investigation.