类风湿关节炎中抗瓜氨酸化蛋白抗体谱：与间质性肺病相关的新自身抗体证据。
Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease.
机构信息
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.
出版信息
Ann Rheum Dis. 2020 May;79(5):587-594. doi: 10.1136/annrheumdis-2019-216709. Epub 2020 Mar 10.
OBJECTIVE
To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.
目的
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。
方法
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。
结果
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。
结论
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。
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