{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:57:25Z","timestamp":1790690245590,"version":"4.1.0"},"reference-count":41,"publisher":"The Journal of Rheumatology","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>The nuclear factor-\u03baB (NF-\u03baB) family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-\u03baB\u2013inducing kinase (NIK) is a key regulator of inflammation-induced angiogenesis in rheumatoid arthritis (RA) synovial tissue (ST). Here, we investigated synovial NIK expression in patients with early arthritis and in autoantibody-positive individuals at risk of developing RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>ST biopsies were obtained by arthroscopy from 154 patients with early arthritis (duration &lt; 1 yr) with various diagnoses and 54 IgM rheumatoid factor\u2013positive and\/or anticitrullinated protein antibodies\u2013positive individuals without evidence of arthritis. ST was stained for NIK and endothelial cell (EC) markers. Additionally, measures of disease activity were collected and contrast-enhanced magnetic resonance imaging (MRI) was performed in a subset of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>In patients with early arthritis, NIK was predominantly expressed in EC of small blood vessels. Further, NIK expression correlated with erythrocyte sedimentation rate (r 0.184, p = 0.024), C-reactive protein (r 0.194, p = 0.017), joint swelling (r 0.297, p &lt; 0.001), synovial immune cell markers (lining r 0.585, p &lt; 0.001; sublining macrophages r 0.728, p &lt; 0.001; T cells r 0.733, p &lt; 0.001; and B cells r 0.264, p = 0.040), MRI effusion (r 0.665, p &lt; 0.001), MRI synovitis (r 0.632, p &lt; 0.001), and MRI total score (r 0.569, p &lt; 0.001). In 18.5% of autoantibody-positive individuals, ST NIK<jats:sup>+<\/jats:sup>EC were present, but this was not predictive of the development of arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>NIK<jats:sup>+<\/jats:sup>EC are present in the earliest phase of synovial inflammation and may be indicative of high angiogenic activity in the inflamed ST. Therefore, NIK<jats:sup>+<\/jats:sup>EC may play an important role in the persistence of synovitis. Collectively, our data underscore the importance of angiogenesis in synovial inflammation and identify NIK as a potential therapeutic target in arthritis.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.150245","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T01:10:43Z","timestamp":1437009043000},"page":"1573-1581","source":"Crossref","is-referenced-by-count":27,"title":["Nuclear Factor-\u03baB\u2013inducing Kinase Is Expressed in Synovial Endothelial Cells in Patients with Early Arthritis and Correlates with Markers of Inflammation: A Prospective Cohort Study"],"prefix":"10.3899","volume":"42","author":[{"given":"Karen I.","family":"Maijer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae Ri","family":"Noort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.H.","family":"de Hair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"van der Leij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katinka P.M.","family":"van Zoest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy Y.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle M.","family":"Gerlag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul P.","family":"Tak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander 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