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Development of auto...
Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
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- Albrecht, Inka (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden.
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- Wick, Cecilia (author)
- Karolinska Institutet
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- Hallgren, Asa (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Expt Endocrinol, SE-17176 Stockholm, Sweden.
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- Tjarnlund, Anna (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden.
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- Nagaraju, Kanneboyina (author)
- Childrens National Medical Centre, DC 20010 USA,Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
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- Andrade, Felipe (author)
- Johns Hopkins University, MD 21205 USA,Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
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- Thompson, Kathryn (author)
- Childrens National Medical Centre, DC 20010 USA,Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
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- Coley, William (author)
- Childrens National Medical Centre, DC 20010 USA,Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
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- Phadke, Aditi (author)
- Childrens National Medical Centre, DC 20010 USA,Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
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- Diaz-Gallo, Lina-Marcela (author)
- Karolinska Institutet
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- Bottai, Matteo (author)
- Karolinska Institutet
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- Nennesmo, Inger (author)
- Karolinska Institutet
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- Chemin, Karine (author)
- Karolinska Institutet
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- Herrath, Jessica (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden.
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- Johansson, Karin (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden.
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- Wikberg, Anders (author)
- Karolinska Institute, Sweden,Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden.
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- Jimmy Ytterberg, A. (author)
- Karolinska Institutet
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- Zubarev, Roman A. (author)
- Karolinska Institutet
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- Danielsson, Olof (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Div Neurol, Linkoping, Sweden.
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- Krystufkova, Olga (author)
- Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic,Charles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Fac Med 1, Dept Rheumatol, Prague, Czech Republic.
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- Vencovsky, Jiri (author)
- Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic,Charles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Fac Med 1, Dept Rheumatol, Prague, Czech Republic.
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- Landegren, Nils (author)
- Karolinska Institutet,Uppsala universitet,Autoimmunitet,Karolinska Inst, Dept Med Solna, Expt Endocrinol, SE-17176 Stockholm, Sweden.
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- Wahren-Herlenius, Marie (author)
- Karolinska Institutet
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- Padyukov, Leonid (author)
- Karolinska Institutet
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- Kämpe, Olle (author)
- Karolinska Institutet,Uppsala universitet,Autoimmunitet,Karolinska Inst, Dept Med Solna, Expt Endocrinol, SE-17176 Stockholm, Sweden.
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- Lundberg, Ingrid E. (author)
- Karolinska Institutet
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Karolinska Institute, Sweden Karolinska Inst, Dept Med Solna, Theumatol Unit, SE-17176 Stockholm, Sweden (creator_code:org_t)
- AMER SOC CLINICAL INVESTIGATION INC, 2015
- 2015
- English.
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In: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 125:12, s. 4612-4624
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Albrecht, Inka
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Wick, Cecilia
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Hallgren, Asa
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Tjarnlund, Anna
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Nagaraju, Kanneb ...
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Andrade, Felipe
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show more...
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Thompson, Kathry ...
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Coley, William
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Phadke, Aditi
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Diaz-Gallo, Lina ...
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Bottai, Matteo
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Nennesmo, Inger
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Chemin, Karine
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Herrath, Jessica
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Johansson, Karin
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Wikberg, Anders
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Jimmy Ytterberg, ...
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Zubarev, Roman A ...
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Danielsson, Olof
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Krystufkova, Olg ...
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Vencovsky, Jiri
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Landegren, Nils
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Wahren-Herlenius ...
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Padyukov, Leonid
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Kämpe, Olle
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Lundberg, Ingrid ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Journal of Clini ...
- By the university
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Linköping University
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Uppsala University
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Karolinska Institutet