Inflammatory myopathies

TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair

Rheumatology (Oxford)Published Mechanistic study

An erratum to this article was published (Rheumatology (Oxford), 2 Nov 2023 ↗)

Authors' conclusion

TWEAK/Fn14 signalling was activated in IMNM, most likely aggravating muscle damage via amplifying inflammatory response and macrophages chemotaxis. Fn14 seems to be a biomarker for assessing disease severity in IMNM.

Study context

Population
Patients with immune-mediated necrotizing myopathy (IMNM) and controls; muscle biopsies, serum and cultured human muscle cells
Participants
37 vs 11
Comparison
IMNM muscle biopsies vs controls
  • IMNMn = 37
  • Controlsn = 11reference
Outcome
Role of TWEAK/Fn14 in IMNM
Methodological detailsin vitro TWEAK treatment of human muscle cells, immunostaining and quantitative PCR, serum ELISA
  • In vitro TWEAK treatment of human muscle cells
  • Immunostaining and quantitative PCR
  • Serum ELISA

Main finding

As reported in the abstract

  • TWEAK and Fn14 overexpressed in IMNM muscle biopsies
  • % Fn14-positive myofibers correlated with disease severity, myonecrosis, regeneration and inflammation infiltrates
  • Fn14-positive myofibers tended to be surrounded or invaded by CD68+ macrophages
  • TWEAK treatment harmful to cultured muscle cells, inducing multiple chemokines and pro-inflammatory cytokines
  • Serum Fn14 increased in IMNM and correlated with muscle weakness

Original publication

TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair. Rheumatology (Oxford). Published 14 March 2023. doi:10.1093/rheumatology/kead108

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