P 41 Mitochondrial pathology in PM-Mito and sIBM

Abstract

Introduction Polymyositis with mitochondrial pathology (PM-Mito) ( Temiz et al., 2009 ) comprises a subgroup of inflammatory myopathies whose pathophysiological and clinical significance is not clear. Besides the lymphocytic infiltrates the PM-Mito ( Siepmann et al., 2013 ) shares the histological finding of mitochondrial abnormalities with the sporadic inclusion body myositis (sIBM), in particular the occurrence of cytochrome-C-oxydase (COX)-deficient muscle fibres and subsarkolemmal accumulation of mitochondria ( Rygiel et al., 2016 , Lindgren et al., 2015 ). Methods We wished to analyze the mitochondrial disturbances in 7 patients with PM-Mito regarding their histological and genetical presentation and compared our findings those obtained from 18 patients with sIBM. Results The age of the PM-Mito patients at the time of the muscle biopsy was 57 ± 10 years and therefore slightly younger than in the sIBM patients (64 ± 9 years), not statistically significant. The disease duration of both groups showed to be identical with 4.6 years. There was no significant difference in the number of COX-deficient muscle fibres between the PM-Mito patients (23 ± 19%) and the patients with sIBM (17 ± 21%), p = 0.52. However, in the long range PCR only in 3/7 PM-Mito patients a weak detection of multiple deletions of the mitochondrial DNA (mtDNA) was obtained. In contrast multiple deletions were significantly more frequent in sIBM patients (p = 0.032): 14/18 had a marked exposition of multiple mitochondrial deletions, 2/18 patients presented with a weak and 2/18 with no evidence of multiple deletions of the mtDNA. Conclusion PM-Mito patients and sIMB patients had both a high number of COX-deficient muscle fibres in their muscle biopsies. But in contrast to the findings in sIBM, the PM-Mito patients presented significantly with lower levels of multiple deletions of the mtDNA. The difference suggests another pathomechanism for the developement of COX-deficiency of muscle fibres in PM-patients as it may result from nuclear mutations in the complex IV of the respiratory chain or non-genetic influences.