Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis–Associated Interstitial Lung Disease

Abstract

Objectives: to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: we performed a nested prospective observational case–control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. Results: the study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17–5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24–6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00–1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00–1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00–1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07–1.46]; p = 0.004). Conclusion: inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.

From Pathogenesis to Treatment—New Perspectives in Rheumatology

“…The study found higher disease activity, according to the Disease Activity Score with Erythrocyte Sedimentation Rate (DAS28-ESR), to be a constant in patients with RA-ILD, as well as higher titers of anti-citrullinated peptide antibodies (ACPA). This data are in line with results from various other studies [1]. Several cytokines and chemokines, such monocyte chemoattractant protein 1 (MCP-1), also known as C-C motif ligand 2 (CCL2), stromal cell-derived factor 1 alpha (SDF-1 alpha), and interleukin-18 (IL-18), were investigated for their correlation with RA-ILD.…”

“…In a nested prospective observational case-control study, Mena-Vázquez et al [1] analyzed various potential biomarkers that may change the approach to the diagnosis and follow-up of rheumatoid arthritis-interstitial lung disease (RA-ILD) and lessen the respiratory burden of rheumatoid arthritis (RA). The authors evaluated the cytokine and inflammation levels in patients diagnosed with RA-ILD compared to patients with RA, but not interstitial lung disease (ILD).…”

Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention

“…Chen et al showed that the baseline titers of RF were significantly higher in patients with progressive RA-ILD, and changes in serum levels of CXCL11 and MMP-13 over 5 years were significantly associated with the progression of RA-ILD [73]. Identifying RA-ILD patients with a progressive phenotype at an early stage can be facilitated through the identification of elevated anti-citrullinated peptide antibody (ACPA) levels, since its presence is associated with high morbidity and mortality [105]. In addition, KL-6 is a circulating marker that is also relevant for diagnosis and for progression in patients with RA-ILD.…”

The Lung in Rheumatoid Arthritis—Friend or Enemy?

“…Regarding other cytokines, IL-4 and IL-18 are also elevated in the serum of patients with ILD [42,158]. In addition, IL-13 is high, being associated with lung fibrosis in HRCT [159][160][161][162][163].…”