title: Complement-mediated muscle cell lysis: a possible mechanism of myonecrosis in anti-SRP associated necrotizing myopathy (ASANM).
abstract: The mechanism of necrotizing myopathy associated with antibodies to signal recognition particle (SRP) remains unclear. We investigated the effect of anti-SRP+serum and complement on cell viability in myoblast cultures. Cell viability was only slightly reduced by incubation with anti-SRP+serum compared with control serum. However, the addition of fresh complement resulted in a marked reduction in cell survival. Surface immunostaining for SRP, C3c and C5b-9 was demonstrated in cultures pre-incubated with anti-SRP+serum and complement, and in muscle biopsies from patients with myopathy. These findings provide further support for a complement-dependent antibody-mediated mechanism in anti-SRP associated myopathy.
authors.affiliation: Australian Neuro-muscular Research Institute and Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Queen Elizabeth II Medical Centre, Perth, WA, Australia.
authors.forename: Arada
authors.initials: A
authors.lastname: Rojana-udomsart
authors.forename: Chalermchai
authors.initials: C
authors.lastname: Mitrpant
authors.forename: Christine
authors.initials: C
authors.lastname: Bundell
authors.forename: Loren
authors.initials: L
authors.lastname: Price
authors.forename: Yue-Bei
authors.initials: YB
authors.lastname: Luo
authors.forename: Victoria
authors.initials: V
authors.lastname: Fabian
authors.forename: Steve D
authors.initials: SD
authors.lastname: Wilton
authors.forename: Peter
authors.initials: P
authors.lastname: Hollingsworth
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood*; D002470:Cell Survival; D002478:Cells, Cultured; D015932:Complement C3c / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D018271:Signal Recognition Particle / Q000276:immunology*
chemical_list: D000906:Antibodies; D018271:Signal Recognition Particle; D015932:Complement C3c
keywords: Anti-SRP antibody; Complement mediated cell lysis; Necrotizing myopathy