Abstract
BackgroundPrevious studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD.MethodsBlood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.ResultsSerum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = − 0.354), total lung capacity (TLC%) (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.ConclusionSerum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.
Highlights
Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA)
Clinical characteristics of patients with RA‐interstitial lung disease (ILD) One hundred and thirty-two individuals were included in this study, including 58 with related interstitial lung disease (RA-ILD), 29 with RA but not ILD (RA-non-ILD), and 45 healthy controls (HC)
The RA-ILD group had a higher positive rate and increased level of anti-cyclic citrullinated peptide (CCP) (93.1% vs 75.0%, P = 0.008 and 696.9 ± 531.4 vs 429.3 ± 555.8, P = 0.004, respectively), but there were no significant differences for rheumatoid factor (RF), anti-nuclear, anti-ds-DNA, anti-Sjögren’s-syndromerelated antigen A, and anti-Ro52 antibody levels between the two disease subgroups
Summary
Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease that causes inflammation and bone destruction in joint areas. Rheumatoid arthritis-related interstitial lung disease (RA-ILD) has been an increasingly recognized disease. It is the main cause of death in rheumatoid arthritis (RA) patients. The etiology of RA-ILD is still unclear, but may be related to smoking, oxidative stress, and other factors that activate autoimmunity and the attack of post-transcriptionally modified self-proteins, such as citrullinated peptides. This phenomenon usually occurs in the synovial tissue of joints. The early identification of RAILD in patients is critical
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