Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Med Solna, Expt Endocrinol, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden..
Visa övriga samt affilieringar
2015 (Engelska)Ingår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 125, nr 12, s. 4612-4624Artikel i tidskrift (Refereegranskat) Published
Resurstyp
Text
Abstract [en]

Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.

Ort, förlag, år, upplaga, sidor
2015. Vol. 125, nr 12, s. 4612-4624
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:uu:diva-270945DOI: 10.1172/JCI81031ISI: 000365831300026PubMedID: 26551678OAI: oai:DiVA.org:uu-270945DiVA, id: diva2:890900
Forskningsfinansiär
VetenskapsrådetRagnar Söderbergs stiftelseKarolinska Institutets ForskningsstiftelseReumatikerförbundetStockholms läns landstingKarolinska Institutets ForskningsstiftelseTorsten Söderbergs stiftelseTillgänglig från: 2016-01-05 Skapad: 2016-01-05 Senast uppdaterad: 2018-01-10Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Sök vidare i DiVA

Av författaren/redaktören
Landegren, NilsKämpe, Olle
Av organisationen
Autoimmunitet
I samma tidskrift
Journal of Clinical Investigation
Immunologi inom det medicinska området

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 694 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf