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Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis
de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (reumatologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Autoimmuna sjukdomar (Kämpe))
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. (Ludwig)
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2009 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 4, 1137-1144 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc. METHODS: Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center. RESULTS: Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal. CONCLUSION: The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.

Place, publisher, year, edition, pages
2009. Vol. 60, no 4, 1137-1144 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-104332DOI: 10.1002/art.24381ISI: 000265152800028PubMedID: 19333949OAI: oai:DiVA.org:uu-104332DiVA: diva2:219666
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved

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Wikström, Gerhard

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