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Multifunctional T c...
Multifunctional T cell reactivity with native and glycosylated type II collagen in rheumatoid arthritis
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- Snir, Omri (författare)
- Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
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- Bäcklund, Johan (författare)
- Karolinska Institutet
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- Boström, Julia (författare)
- Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
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- Andersson, Ida (författare)
- Umeå universitet
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- Kihlberg, Jan (författare)
- Umeå universitet
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- Buckner, Jane H. (författare)
- Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
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- Klareskog, Lars (författare)
- Karolinska Institutet
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- Holmdahl, Rikard (författare)
- Karolinska Institutet
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- Malmström, Vivianne (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-07-27
- 2012
- Engelska.
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Ingår i: Arthritis and Rheumatism. - : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 64:8, s. 2482-2488
- Relaterad länk:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Objective Type II collagen (CII) is a cartilage-specific protein to which a loss of immune tolerance may trigger autoimmune reactions and cause arthritis. The major T cell epitope on CII, amino acids 259273, can be presented by several HLADRB1*04 alleles in its native or posttranslational glycosylated form. The present study was undertaken to functionally explore and compare CII-autoreactive T cells from blood and synovial fluid of patients with rheumatoid arthritis (RA).Methods Peripheral blood was obtained from HLADRB1*04positive RA patients (n = 10) and control subjects (n = 10) and stimulated in vitro with several variants of the CII259273 epitope, i.e., unmodified, glycosylated on Lys-264, glycosylated on Lys-270, or glycosylated on both Lys-264 and Lys-270. Up-regulation of CD154 was used to identify responding T cells. These cells were further characterized by intracellular staining for interleukin-17 (IL-17), interferon-? (IFN?), and IL-2 by flow cytometry. Synovial T cells from RA patients were investigated in parallel.Results Multifunctional T cell responses toward all examined variants of the CII259273 peptide could be detected in RA patients and, to a lesser extent, also in healthy HLA-matched controls (P < 0.001). In RA patients, a comparison between blood- and joint-derived T cell function revealed a significant increase in levels of the proinflammatory cytokine IFN? in synovial T cells (P = 0.027). Studies of longitudinally obtained samples showed that T cell responses were sustained over the course of disease, and even included epitope spreading.Conclusion The identification of inflammatory T cell responses to both glycosylated and nonglycosylated variants of the major CII epitope in RA patients suggests that CII autoreactivity in RA may be more common than previously recognized.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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