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Sohrabian, AzitaUppsala universitet,Klinisk immunologi
(author)
Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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2018-06-12
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BMJ,2018
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-363389
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-363389URI
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https://doi.org/10.1136/annrheumdis-2017-212627DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:139151372URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Introduction: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.Methods: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.Results: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.Conclusions: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.
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Mathsson Alm, LindaUppsala universitet,Klinisk immunologi(Swepub:uu)limat990
(author)
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Hansson, MonikaKarolinska Institutet
(author)
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Knight, AnnUppsala universitet,Reumatologi(Swepub:uu)ankni172
(author)
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Lysholm, JörgenFalun Cent Hosp, Clin Rheumatol, Falun, Sweden
(author)
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Cornillet, MartinToulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France
(author)
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Skriner, KarlCharite, Dept Med, Berlin, Germany
(author)
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Serre, GuyToulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France
(author)
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Larsson, AndersUppsala universitet,Klinisk kemi(Swepub:uu)andlarss
(author)
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Weitoft, TomasUppsala universitet,Centrum för klinisk forskning, Gävleborg(Swepub:uu)tomwe626
(author)
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Rönnelid, JohanUppsala universitet,Klinisk immunologi(Swepub:uu)joharonn
(author)
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Uppsala universitetKlinisk immunologi
(creator_code:org_t)
Related titles
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In:Annals of the Rheumatic Diseases: BMJ77:9, s. 1345-13530003-49671468-2060
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Sohrabian, Azita
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Mathsson Alm, Li ...
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Hansson, Monika
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Knight, Ann
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Lysholm, Jörgen
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Cornillet, Marti ...
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Skriner, Karl
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Serre, Guy
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Larsson, Anders
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Weitoft, Tomas
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Rönnelid, Johan
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Rheumatology and ...
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Uppsala University
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Karolinska Institutet