@article {Maijerjrheum.150245, author = {Karen I. Maijer and Ae Ri Noort and Maria J.H. de Hair and Christiaan van der Leij and Katinka P.M. van Zoest and Ivy Y. Choi and Dani{\"e}lle M. Gerlag and Mario Maas and Paul P. Tak and Sander W. Tas}, title = {Nuclear Factor-κB{\textendash}inducing Kinase Is Expressed in Synovial Endothelial Cells in Patients with Early Arthritis and Correlates with Markers of Inflammation: A Prospective Cohort Study}, elocation-id = {jrheum.150245}, year = {2015}, doi = {10.3899/jrheum.150245}, publisher = {The Journal of Rheumatology}, abstract = {Objective The nuclear factor-κB (NF-κB) family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-κB{\textendash}inducing 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. Methods ST biopsies were obtained by arthroscopy from 154 patients with early arthritis (duration \< 1 yr) with various diagnoses and 54 IgM rheumatoid factor{\textendash}positive and/or anticitrullinated protein antibodies{\textendash}positive 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. Results 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 \< 0.001), synovial immune cell markers (lining r 0.585, p \< 0.001; sublining macrophages r 0.728, p \< 0.001; T cells r 0.733, p \< 0.001; and B cells r 0.264, p = 0.040), MRI effusion (r 0.665, p \< 0.001), MRI synovitis (r 0.632, p \< 0.001), and MRI total score (r 0.569, p \< 0.001). In 18.5\% of autoantibody-positive individuals, ST NIK+EC were present, but this was not predictive of the development of arthritis. Conclusion NIK+EC are present in the earliest phase of synovial inflammation and may be indicative of high angiogenic activity in the inflamed ST. Therefore, NIK+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.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/early/2015/07/10/jrheum.150245}, eprint = {https://www.jrheum.org/content/early/2015/07/10/jrheum.150245.full.pdf}, journal = {The Journal of Rheumatology} }