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Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation
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2015 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, no 9, 1772-1777 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Immunological events in the lungs might trigger production of anti-citrullinated protein antibodies during early rheumatoid arthritis (RA). We investigated the presence of shared immunological citrullinated targets in joints and lungs of patients with RA.

PATIENTS AND METHODS: Proteins extracted from bronchial (n=6) and synovial (n=7) biopsy specimens from patients with RA were investigated by mass spectrometry-based proteomics. One candidate peptide was synthesised and used to investigate by ELISA the presence of antibodies in patients with RA (n=393), healthy controls (n=152) and disease controls (n=236). HLA-DRB1 shared epitope (SE) alleles were detected in patients with RA.

RESULTS: Ten citrullinated peptides belonging to seven proteins were identified, with two peptides shared between the synovial and bronchial biopsy samples. Further analysis, using accurate mass and retention time, enabled detection of eight citrullinated peptides in synovial and seven in bronchial biopsy specimens, with five peptides shared between the synovial and bronchial biopsy specimens. Two citrullinated vimentin (cit-vim) peptides were detected in the majority of synovial and lung tissues. Antibodies to a synthesised cit-vim peptide candidate (covering both cit-vim peptides identified in vivo) were present in 1.8% of healthy controls, 15% of patients with RA, and 3.4% of disease controls. Antibodies to cit-vim peptide were associated with the presence of the SE alleles in RA.

CONCLUSIONS: Identical citrullinated peptides are present in bronchial and synovial tissues, which may be used as immunological targets for antibodies of patients with RA. The data provide further support for a link between lungs and joints in RA and identify potential targets for immunity that may mediate this link.

Place, publisher, year, edition, pages
2015. Vol. 74, no 9, 1772-1777 p.
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-239509DOI: 10.1136/annrheumdis-2013-204912ISI: 000359378100028PubMedID: 24817415OAI: oai:DiVA.org:uu-239509DiVA: diva2:774769
Funder
Swedish Foundation for Strategic Research EU, FP7, Seventh Framework Programme, 305549-2Swedish Research CouncilSwedish Heart Lung FoundationStockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2014-12-29 Created: 2014-12-29 Last updated: 2017-12-05Bibliographically approved

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Rönnelid, Johan

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