Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory myopathies.
We studied mitochondrial function in inflammatory myopathies, using cytochrome c oxidase (COX) reaction on muscle biopsy samples from 30 patients (15 with dermatomyositis, 12 with polymyositis, and 3 with inclusion body myositis) and 30 age-matched controls. We also performed immunocytochemistry for COX II and COX IV subunits in 7 of these patients who had COX deficiency. COX-deficient fibers were a constant finding in patients or controls older than 65 years and the percentage of COX-deficient fibers correlated with age in both patients and controls. Focal COX deficiency was found in 24 patients (13 of 15 with dermatomyositis, 8 of 12 with polymyositis, and 3 of 3 with inclusion body myositis) and 18 controls. The percentages of COX-deficient fibers were higher in patients with inflammatory myopathies (range: 0-4.7%; mean: 1.2%) than in age-matched controls (range: 0-1.9%; mean: 0.4%) (P < 0.01). In the subgroup of patients under age 65, COX-deficient fibers were more frequent in dermatomyositis than in polymyositis (mean: 0.8% vs 0.2%, P = 0.02). In patients with dermatomyositis, capillary loss correlated positively with COX deficiency (P < 0.02). Immunocytochemistry for COX II and IV showed that 82% of COX-negative fibers were COX II-negative and 26% were COX IV-negative, suggesting that proteins encoded by mitochondrial DNA are predominantly, but not exclusively, involved in COX deficiency. We conclude that mitochondrial dysfunction and COX deficiency can occur in inflammatory myopathies. Such a mitochondrial dysfunction is not solely related to the aging process. We suggest that muscle ischemia contributes to mitochondrial dysfunction in dermatomyositis.
Chariot
P
P
Department of Pathology, Hôpital Henri Mondor, Créteil, France.
Ruet
E
E
Authier
F J
FJ
Labes
D
D
Poron
F
F
Gherardi
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000473:pathology; D002648:Child; D030401:Cytochrome-c Oxidase Deficiency; D003882:Dermatomyositis / Q000201:enzymology / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D018979:Myositis, Inclusion Body / Q000201:enzymology / Q000473:pathology*; D017285:Polymyositis / Q000201:enzymology / Q000473:pathology*