Weitoft Tomas, Rönnelid Johan, Lind Anders, de Vries Charlotte, Larsson Anders, Potempa Barbara, Potempa Jan, Kastbom Alf, Martinsson Klara, Lundberg Karin, Högman Marieann
Centre for Research and Development, Uppsala University, Region Gävleborg, 801 88 Gävle, Sweden.
Rheumatology, Department of Medical Science, Uppsala University, 751 85 Uppsala, Sweden.
Biomedicines. 2024 Apr 26;12(5):964. doi: 10.3390/biomedicines12050964.
Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman-Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho -0.48, = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho -0.41, = 0.017), between the alveolar concentration and free secretory component (Rho -0.35, = 0.023) and between the alveolar concentration and C-reactive protein (Rho -0.36, = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.
与健康对照相比,类风湿性关节炎(RA)患者呼出的一氧化氮(NO)水平有所改变。在此,我们研究了RA发病机制中的临床特征和免疫因素是否与疾病早期的NO肺动力学相关。共纳入了44例早期RA且抗瓜氨酸化肽抗体(ACPA)呈阳性(具体为环瓜氨酸化肽2[CCP2])的患者。测量了他们呼出的NO水平,并使用Högman-Meriläinen算法估算了肺泡浓度、气道隔室扩散能力以及NO的气道壁浓度。使用28个关节的疾病活动评分来测量疾病活动度。分析血清样本中的抗CCP2、类风湿因子、游离分泌成分、含ACPA的分泌成分、抗(Rgp)抗体以及IgA、IgA1和IgA2的总水平。发现NO的气道壁浓度与肿胀关节数量之间存在显著负相关(Rho -0.48, = 0.004),NO的气道壁浓度与IgA类风湿因子之间存在显著负相关(Rho -0.41, = 0.017),肺泡浓度与游离分泌成分之间存在显著负相关(Rho -0.35, = 0.023),肺泡浓度与C反应蛋白之间存在显著负相关(Rho -0.36, = 0.016),但抗CCP2、IgM类风湿因子或抗Rgp水平之间未发现相关性。总之,NO水平的改变,尤其是其在气道壁中的产生,可能在ACPA阳性RA的发病机制中起作用。