目的:转录因子核因子-κB(NF-κB)家族与滑膜炎症密切相关。我们先前已经证明NF-κB诱导激酶(NIK)是类风湿性关节炎(RA)滑膜组织(ST)中炎症诱导的血管生成的关键调节剂。这里,我们调查了早期关节炎患者和自身抗体阳性个体的滑膜NIK表达。
方法:通过关节镜检查从154例早期关节炎(持续时间<1年)患者中获得了ST活检,这些患者具有不同的诊断和54例IgM类风湿因子阳性和/或抗瓜氨酸蛋白抗体阳性个体,没有关节炎的证据。对NIK和内皮细胞(EC)标记物进行ST染色。此外,我们收集了疾病活动度测量值,并对这些患者的一部分进行了对比增强磁共振成像(MRI).
结果:在早期关节炎患者中,NIK主要在小血管EC中表达。Further,NIK表达与红细胞沉降率相关(r0.184,p=0.024),C反应蛋白(r0.194,p=0.017),关节肿胀(r0.297,p<0.001),滑膜免疫细胞标记(衬里r0.585,p<0.001;亚衬巨噬细胞r0.728,p<0.001;T细胞r0.733,p<0.001;B细胞r0.264,p=0.040),MRI积液(r0.665,p<0.001),MRI滑膜炎(r0.632,p<0.001),MRI总分(r0.569,p<0.001)。在18.5%的自身抗体阳性个体中,出现STNIK(+)EC,但这并不能预测关节炎的发展。
结论:NIK(+)EC存在于滑膜炎症的最早阶段,可能表明炎症ST段血管生成活性高。因此,NIK(+)EC可能在滑膜炎的持续存在中起重要作用。总的来说,我们的数据强调了血管生成在滑膜炎症中的重要性,并确定NIK是关节炎的潜在治疗靶点.
OBJECTIVE: The nuclear factor-κB (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). 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-positive and/or anticitrullinated protein antibodies-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.
CONCLUSIONS: 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.