Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies.
Antibody-dependent complement-mediated muscle fiber injury is a hypothetical immune effector response in inflammatory muscle diseases. Moreover, a sarcolemmal alteration in muscular dystrophies might trigger antibody-independent activation of the alternative complement pathway. We therefore searched for C5b9 complement membrane attack complex (MAC), immunoglobulin (Ig)G, and IgM deposits on nonnecrotic muscle fibers in muscle specimens from 81 patients with inflammatory myopathies, 45 patients with muscular dystrophies, and 19 patients with necrotizing myopathies. Sarcolemmal MAC deposits were present on nonnecrotic fibers (C+ fibers) in only two unusual types of inflammatory myopathy. By contrast, seven of 17 facioscapulohumeral dystrophy, four of nine limb-girdle dystrophy, and three of six merosin (laminin-alpha-2)-positive congenital muscular dystrophy but none of the Becker or Duchenne dystrophy specimens harbored C+ fibers. None of the C+ fibers immunostained for IgG or IgM, and none failed to immunostain for CD59 or CD46-inhibitors of the complement cascade. Our findings do not support a role for antibody-dependent complement-mediated muscle fiber injury in the major inflammatory muscle diseases. The cause and pathogenetic significance of the C+ fibers in the different types of muscular dystrophies remains to be elucidated.
Spuler
S
S
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Engel
A G
AG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D018957:CD59 Antigens / Q000032:analysis / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000032:analysis / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000032:analysis* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D009136:Muscular Dystrophies / Q000276:immunology* / Q000473:pathology*; D009336:Necrosis; D017285:Polymyositis / Q000276:immunology / Q000473:pathology; D012508:Sarcolemma / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; C497857:CD46 protein, human; D018957:CD59 Antigens; D003176:Complement C3; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins