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  • 1
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2020-12)
    Abstract: 14-3-3η is an intracellular protein also detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA). It is closely related to disease activity and anti-cyclic citrullinated peptide antibody levels. However, the main source of 14-3-3η and the mechanism of its release into the extracellular space remain unclear. Addressing these two points was the main goal of the current study. Methods The source of 14-3-3η was investigated by immunostaining RA synovial tissue. Fibroblast-like synoviocytes, CD4 + cells, and macrophages were selected as candidates among the various cell types in the synovial tissue. Phosphorylation of mixed-lineage kinase domain-like pseudokinase (MLKL) and cell death of macrophages were studied by phalloidin staining and electron microscopy after stimulation with an oxidative stress inducer (diamide) or tumour necrosis factor (TNF)-α. Extracellular 14-3-3η protein levels were examined by western blotting. Results Macrophages from the synovial tissue from RA, but not osteoarthritis, showed dense and widespread cytoplasmic staining for the 14-3-3η protein, co-localized with peptidylarginine deiminase 4. Swelling and membrane rupture of macrophages were induced by treatment with TNF-α, but not interleukin (IL) 6/soluble IL-6 receptor (sIL-6R). Increased MLKL phosphorylation followed by necroptosis was also induced in TNF-α-stimulated macrophages. Necrostatin-1, a necroptosis inhibitor, antagonized MLKL phosphorylation. High levels of 14-3-3η were detected in the culture supernatants of macrophages stimulated with diamide and TNF-α, but not IL-6/sIL-6R. Conclusions Macrophages that highly express 14-3-3η undergo TNF-α-induced necroptosis with damage to the cellular structure, resulting in the secretion of 14-3-3η into the extracellular space. The current study provides a novel mechanism for 14-3-3η level increase in the RA synovial fluid.
    Type of Medium: Online Resource
    ISSN: 1478-6362
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041668-4
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  • 2
    Online Resource
    Online Resource
    Informa UK Limited ; 2021
    In:  Open Access Rheumatology: Research and Reviews Vol. Volume 13 ( 2021-04), p. 63-71
    In: Open Access Rheumatology: Research and Reviews, Informa UK Limited, Vol. Volume 13 ( 2021-04), p. 63-71
    Type of Medium: Online Resource
    ISSN: 1179-156X
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2508169-X
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  • 3
    In: RMD Open, BMJ, Vol. 6, No. 1 ( 2020-05), p. e001191-
    Abstract: To evaluate biomarkers as predictors of impending erosion progression. Methods Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations. Results Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP). Conclusions Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.
    Type of Medium: Online Resource
    ISSN: 2056-5933
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2812592-7
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  • 4
    In: Arthritis Care & Research, Wiley, Vol. 76, No. 4 ( 2024-04), p. 444-453
    Abstract: The objective was to understand how the expansion of rheumatology supply and the introduction of multidisciplinary care was associated with access to rheumatology services. Methods We accessed Population Data BC, a longitudinal database with de‐identified individual‐level health data on all residents of British Columbia, Canada, to analyze physician visits and prescribing from 2010–2011 to 2019–2020. We calculated access as the time from referral to first rheumatologist visit and, for people with rheumatoid arthritis (RA), time to first disease‐modifying antirheumatic drug (DMARD). Associations between lag time, patient characteristics, and system variables were explored using quantile regression. Results Over the study period, there were 149,902 new rheumatologist visits, with 31% more visits in 2019–2020 than in 2010–2011. The proportion of first visits for patients with inflammatory arthritis increased from 28% to 51%. The median time from referral to first visit decreased by 22 days (35%) from 63 days (interquartile range 21–120 days) in 2010–2011. For people with RA, time from referral to DMARD decreased by 4 days (6%) to 62 days. Male sex, living in metropolitan areas, and having a rheumatologist who used a multidisciplinary care assessment code were associated with shorter times from referral to first DMARD. Conclusion Access to rheumatology care improved, and the increased proportion of patients with IA in the first visits case‐mix indicates that rheumatologist supply and incentives for multidisciplinary care may have improved referral patterns. However, time to DMARDs for people with RA remained long, and we found signals of unequal access for female patients and people living outside of metropolitan areas.
    Type of Medium: Online Resource
    ISSN: 2151-464X , 2151-4658
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2016713-1
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