Necrosis in anti-SRP+ and anti-HMGCR+myopathies: Role of autoantibodies and complement.
Neurology
; 90(6): e507-e517, 2018 02 06.
Article
em En
| MEDLINE
| ID: mdl-29330311
ABSTRACT
OBJECTIVE:
To characterize muscle fiber necrosis in immune-mediated necrotizing myopathies (IMNM) with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its underlying molecular immune mechanisms.METHODS:
Muscle biopsies from patients with IMNM were analyzed and compared to biopsies from control patients with myositis. In addition to immunostaining and reverse transcription PCR on muscle samples, in vitro immunostaining on primary muscle cells was performed.RESULTS:
Creatine kinase levels and muscle regeneration correlated with the proportion of necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune environment were chiefly involved in ongoing myophagocytosis of necrotic fibers. T-cell densities correlated with necrosis but no signs of cytotoxicity were detected. Activation of the classical pathway of the complement cascade, accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was reproduced on myotubes exposed to purified patient-derived autoantibodies. Finally, a correlation between sarcolemmal complement deposits and fiber necrosis was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to update the pathologic criteria of IMNM.CONCLUSION:
These data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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Proteínas do Sistema Complemento
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Partícula de Reconhecimento de Sinal
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Músculo Esquelético
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Hidroximetilglutaril-CoA Redutases
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Doenças Musculares
Tipo de estudo:
Etiology_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article