Amyloid Filaments in Inclusion Body Myositis: Novel Findings Provide Insight Into Nature of Filaments

• Published in: Archives of neurology (Chicago) Vol. 48; no. 12; pp. 1229 - 1234
• Main Authors: Mendell, Jerry R, Sahenk, Zarife, Gales, Tracy, Paul, Laura
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 01.12.1991
• Subjects: Adult; Aged; Amyloid - analysis; Female; Humans; Inclusion Bodies - chemistry; Inclusion Bodies - pathology; Intermediate Filaments - chemistry; Intermediate Filaments - pathology; Male; Middle Aged; Muscular Diseases - metabolism; Muscular Diseases - pathology; Myositis - metabolism; Myositis - pathology; Vacuoles - pathology
• ISSN: 0003-9942; 1538-3687
• DOI: 10.1001/archneur.1991.00530240033013

• Inclusion body myositis (IBM) represents a serious debilitating disease of muscle without identifiable cause or treatment. Muscle biopsy specimens have characteristic rimmed vacuoles, varying degrees of inflammation, and, most importantly, cytoplasmic and intranuclear filamentous inclusions of unknown composition. Fresh-frozen sections of muscle biopsy specimens from 24 IBM cases were stained with Congo red dye (pH, 10.5 to 11.0). Control biopsy specimens included polymyositis, dermatomyositis, hereditary vacuolar myopathies of unknown cause, acid maltase deficiency, distal myopathy, oculopharyngeal dystrophy, and chloroquine myopathy. Sections were also immunostained with antibody to transthyretin, human P component, and immunoglobulin light chains. In the vacuolated fibers in IBM, amyloidogenic green-birefringent deposits were seen. Some deposits were delicate and wispy appearing, and others were plaque-like. The size of deposits varied, measuring 1 × 2 to 8 μm, and rarely up to 20 μm in length. The number of amyloid-positive fibers correlated with the number of vacuolated fibers. Similar deposits were seen in one case of distal myopathy and one hereditary vacuolar myopathy. Other control cases were negative for amyloid deposits. Antibody staining for known amyloidogenic proteins was negative. This study demonstrates that the filaments in IBM share properties with amyloid proteins. The location implies that this amyloid material is formed intracellularly, rather than having a systemic derivation. The association of amyloid deposits with autophagic vacuoles in IBM raises the likely possibility that the filaments represent a modification of a normal protein within an acidic degradative vacuolar compartment. An alternative possibility, considering the shared properties of IBM filaments and prions (which include size and amyloidogenic properties), is that IBM represents a human prion disease. Further studies will be required to resolve the nature of the amyloidogenic filaments in IBM, but these findings may provide clues to the pathogenesis of this poorly understood disorder. In addition, the findings should facilitate the clinical diagnosis of IBM.