Background Interstitial lung disease (ILD) develops in 5–10% of patients with rheumatoid arthritis (RA) and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD. Methods We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for transforming growth factor beta (TGF-β) levels by immunoassay. DNA was extracted to determine presence of the MUC5B ILD-risk allele (“T”). High resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were completed within 3 months of sputum collection and quantified to determine lung disease severity. Results Sputum TGF-β was significantly elevated in individuals with RA-PF compared with RA-no-ILD (p< 0.001) and correlated with more fibrosis on HRCT (p= 0.005) and lower forced vital capacity (p= 0.006) and diffusion capacity of carbon monoxide (p= 0.044) on PFTs. Within RA-PF patients, sputum TGF-β was higher in those with the MUC5B ILD-risk genotype (GT/TT) (p= 0.038). There were no differences in serum levels of TGF-β between groups. Conclusion We demonstrate that sputum levels of TGF-β are significantly elevated in individuals with RA-PF, correlate with lung disease severity, and are elevated in those with the MUC5B ILD-risk polymorphism. These findings could identify novel approaches to ILD screening in RA and potential targeted therapeutic strategies for RA-ILD.

中文翻译：

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类风湿性关节炎相关肺纤维化患者痰液中的转化生长因子-β 增加


背景 类风湿性关节炎 （RA） 患者有 5-10% 发生间质性肺病 （ILD），并显着导致发病率和死亡率，尤其是在具有纤维化表型的患者中。然而，可靠地识别具有潜在肺纤维化的 RA 患者的生物标志物并不充分。在此，我们使用痰液来识别基于肺的生物标志物，这些生物标志物可以区分具有潜在肺纤维化的 RA 患者，并可能更好地告知 RA-ILD 的潜在发病机制。方法 我们纳入了 37 例伴有肺纤维化的 RA 患者 （RA-PF） 和 30 例无 ILD 的 RA 患者 （RA-no-ILD）。通过免疫测定检测诱导痰液和血清的转化生长因子 β （TGF-β） 水平。提取 DNA 以确定是否存在 MUC5B ILD 风险等位基因 （“T”）。在痰液采集后 3 个月内完成高分辨率计算机断层扫描 （HRCT） 和肺功能测试 （PFT），并量化以确定肺部疾病的严重程度。结果 与 RA-no-ILD 相比，RA-PF 个体的痰液 TGF-β 显著升高 （p< 0.001），并且与 HRCT 纤维化增加 （p=0.005） 和用力肺活量降低 （p=0.006） 和一氧化碳弥散量 （p=0.044） 相关PFTs。在 RA-PF 患者中，MUC5B ILD 风险基因型 （GT/TT） 患者的痰液 TGF-β 较高 （p= 0.038）。血清 TGF-β 水平组间无差异。结论 我们证明 RA-PF 个体痰液中 TGF-β 水平显著升高，与肺部疾病严重程度相关，在 MUC5B ILD 风险多态性患者中升高。这些发现可以确定 RA 中 ILD 筛查的新方法以及 RA-ILD 的潜在靶向治疗策略。