Inflammatory myopathies with mitochondrial pathology and protein aggregates.
OBJECTIVE
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 alphaB-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. beta-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 alphaB-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.
Temiz
Peyker
P
Celal Bayar University School of Medicine, Department of Pathology, Manisa, 45010, Turkey.
Weihl
Conrad C
CC
Pestronk
Alan
A
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001343:Autophagy; D001402:B-Lymphocytes / Q000473:pathology; D001706:Biopsy; D003459:Crystallins / Q000378:metabolism; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000473:pathology*; D018908:Muscle Weakness; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009220:Myositis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D012189:Retrospective Studies
D000305:Adrenal Cortex Hormones; D003459:Crystallins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D003576:Electron Transport Complex IV