Inflammatory myopathies with mitochondrial pathology and protein aggregates
No Thumbnail Available
Date
2009
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Objectives: To compare the clinical course and muscle biopsy features of polymyositis with mitochondrial pathology (PM-Mito) to inclusion body myositis (IBM) and steroid-responsive inflammatory myopathies (polymyositis). Methods: We compared clinical, laboratory and myopathologic features in a retrospective study of patients with PM-Mito (23), IBM (26) and polymyositis (12). Results: Selective weakness in the quadriceps or finger flexors was common in PM-Mito (62%) and IBM (87%). Weakness progressed more slowly in PM-Mito than in IBM. PM-Mito patients with more rapidly progressive weakness had more cytochrome oxidase negative muscle fibers. There was no history of benefit from corticosteroid treatment in any PM-Mito or IBM patients. B-cell foci were absent in IBM and PM-Mito. LC3, an autophagy marker, and αB-crystallin were common in aggregates in PM-Mito and IBM, but not polymyositis. SMI-31 and TDP-43 positive aggregates were common in IBM but not in PM-Mito or polymyositis. β-amyloid showed no differences in aggregates among the three groups. Conclusions: PM-Mito and IBM may be part of the same disease spectrum. PM-Mito has more slowly progressive weakness than IBM and rarely has TDP-43 or SMI-31 staining aggregates in muscle fibers. The most frequent proteins in aggregates in both PM-Mito and IBM are LC3, an autophagy marker, and αB-crystallin. Alterations in autophagic degradation pathways may be a common pathogenic mechanism in PM-Mito and IBM. In pathologically typical polymyositis, staining for mitochondrial enzyme activity, aggregates and B-cells helps to distinguish PM-Mito from inflammatory myopathy syndromes that are more likely to respond to corticosteroid treatment. © 2008 Elsevier B.V. All rights reserved.
Description
Keywords
Adrenal Cortex Hormones , Autophagy , B-Lymphocytes , Biopsy , Crystallins , Disease Progression , Electron Transport Complex IV , Humans , Inclusion Bodies , Microtubule-Associated Proteins , Mitochondria, Muscle , Muscle Weakness , Muscle, Skeletal , Myositis , Retrospective Studies , alpha crystallin , amyloid beta protein , binding protein , biological marker , caveolin 3 , corticosteroid , cytochrome c oxidase , desmin , emerin , mitochondrial enzyme , protein LC3 , protein SMI 31 , TAR DNA binding protein , unclassified drug , adult , article , autophagy , B lymphocyte , comparative study , controlled study , corticosteroid therapy , disease course , disorders of mitochondrial functions , enzyme activity , female , hand muscle , human , human tissue , inclusion body myositis , light chain , major clinical study , male , muscle biopsy , muscle cell , muscle mitochondrion , muscle weakness , polymyositis , priority journal , protein aggregation , quadriceps femoris muscle , retrospective study