Background The NF-κB family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-κB-inducing kinase (NIK) is a key regulator of inflammation-induced angiogenesis in rheumatoid arthritis (RA) synovial tissue (ST).
Objectives In this study we investigated the expression of NIK in ST of early arthritis patients and individuals at risk of developing RA.
Methods Arthroscopic synovial biopsy samples were obtained from early arthritis patients (arthritis duration<1 year, disease modifying anti-rheumatic drug naïve). ST sections were stained for the expression of NIK and evaluated by digital image analysis. In addition, clinical assessment data such as CRP, ESR and swelling of the biopsied joint (score of 0 (no swelling) – 3 (severe swelling)) were collected. In a subset of these patients contrast enhanced MRI was performed in the same joint as ST samples were obtained and scored for hydrops, synovitis, edema, cartilage degeneration and erosions, each in 4-6 compartments. A score of 0-3 for each compartment was given and a total MRI score was calculated (0-81).
Arthroscopic synovial biopsy samples were also obtained from 46 IgM-rheumatoid factor and/or anti-citrullinated peptide antibody positive individuals at risk for developing RA, who never had any evidence of arthritis upon physical examination. ST sections were stained for NIK and evaluated by semi quantitative analyses (positive or negative).
Results 154 Early arthritis patients were included (RA (n=64), unclassified arthritis (n=61), crystal arthropathy (n=11), osteoarthritis (n=4) and spondyloarthritis (n=14)). NIK was predominantly expressed in endothelial cells of small blood vessels as described before. No significant difference was observed in baseline NIK expression between different classification groups. NIK expression correlated with ESR (r=0.214; p=0.006), CRP (r=0.207; p=0.008), swelling of the biopsied joint (r=0.297; p<0.001), MRI hydrops (r=0.648; p<0.001), MRI synovitis (r=0.629; p<0.001) and MRI total score (r=0.568; p<0.001). NIK expression did not significantly correlate with cartilage damage and erosion scores. In autoantibody-positive individuals synovial NIK expression at baseline was not associated with the development of arthritis.
Conclusions We established that synovial NIK expression is associated both with systemic markers of disease activity (ESR and CRP) and with local disease activity in DMARD-naive early arthritis patients, independent of the diagnosis. These findings underscore the importance of angiogenesis in synovial inflammation and identify NIK as a potential therapeutic target in arthritis.
Disclosure of Interest None Declared
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