Rheumatology Department, Arthritis Unit, Hospital Clinic de Barcelona, Barcelona, Spain.
Consejo Superior de Investigaciones Científicas, Unit of Synthesis and Biomedical Applications of Peptides, CSIC-IQAC, Barcelona, Spain.
Ann Rheum Dis. 2020 May;79(5):587-594. doi: 10.1136/annrheumdis-2019-216709. Epub 2020 Mar 10.
To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.
Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.
We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.
Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.
分析抗瓜氨酸化蛋白抗体（Anti-CarP）与类风湿关节炎（RA）患者间质性肺病（ILD）之间的相关性。
本研究为一项包含符合 2010 年 ACR/EULAR 标准的 RA 患者的横断面研究。主要人群包含两组：（1）诊断为 RA-ILD（RA-ILD 组）的 RA 患者；（2）无 ILD 的 RA 患者（非 ILD RA 组）。疑似患有 ILD 的非 ILD RA 患者接受了诊断性检查，如果确诊为 ILD，则将其归入 RA-ILD 组。ILD 通过高分辨率计算机断层扫描诊断，并由多学科委员会确认。还获得了一个独立的复制样本。使用自制 ELISA 测定针对胎牛血清（Anti-FCS）、纤维蛋白原（Anti-Fib）和嵌合纤维蛋白/原纤维蛋白同源半胱氨酸肽（Anti-CFFHP）的三种 Anti-CarP IgG 自身抗体（Anti-FCS）、针对胎牛血清的一种 Anti-CarP IgA（Anti-FCS-IgA）。使用多变量逻辑回归分析调整吸烟、性别、年龄、RA 疾病持续时间、类风湿因子和抗瓜氨酸蛋白抗体后，分析 Anti-CarP 与 ILD 之间的相关性。
共纳入 179 名患者：最终有 37 名（21%）患者被诊断为 RA-ILD。RA-ILD 患者中 Anti-CarP 特异性更为常见（Anti-FCS 70%比 43%；Anti-Fib 73%比 51%；Anti-CFFHP 38%比 19%；Anti-CarP-IgA 51%比 20%，所有比较均 p<0.05）。RA-ILD 患者的 Anti-CarP 血清滴度显著更高。在多变量分析中，Anti-CarP 特异性对增加 ILD 的几率具有显著影响（Anti-FCS（OR：3.42；95%CI：1.13 至 10.40）、Anti-Fib（OR：2.85；95%CI：0.83 至 9.70）、Anti-CFFHP（OR：3.11；95%CI：1.06 至 9.14）和 Anti-FCS-IgA（OR：4.30；95%CI：1.41 至 13.04））。在复制样本中也观察到了类似的发现。
Anti-CarP 与 ILD 密切相关。瓜氨酸化在 RA-ILD 中的作用值得进一步研究。
