Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis.

Previous 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. Blood 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. Serum 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. Serum 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.

Xu L ，Jiang L ，Nie L ，Zhang S ，Liu L ，Du Y ，Xue J ... -  《BMC IMMUNOLOGY》

Increased serum soluble programmed death ligand 1(sPD-L1) is associated with the presence of interstitial lung disease in rheumatoid arthritis: A monocentric cross-sectional study.

This paper is to examine the relationship between serum soluble programmed death ligand 1(sPD-L1) levels and the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Serum sPD-L1 were measured by enzyme-linked immunosorbent assay. sPD-L1 levels in RA with ILD, RA without ILD and healthy controls were compared. Associations between ILD and various markers including sPD-L1 and confounding factors were investigated by logistic regression analysis. Diagnostic values of sPD-L1 for the presence of ILD were investigated using receiver operating characteristics curve analysis. Serum sPD-L1 levels were higher in RA patients with ILD than RA patients without ILD and healthy controls (23.7 ± 9.8 vs. 18.0 ± 7.7 pg/mL, P = 0.01 and 23.7 ± 9.8 vs. 2.9 ± 1.5 pg/mL, P < 0.0001). sPD-L1 levels were positively correlated with RF titer (r = 0.245, P = 0.03), CRP (r = 0.265,P = 0.01), HRCT score (r = 0.265, P = 0.04) and Ferritin (r = 0.442, P = 0.01), but negatively associated with FVC% (r = -0.359, P = 0.01) and DLCO% (r = -0.399, P = 0.008). sPD-L1 and anti-CCP antibody status were independently associated with the presence of ILD during multivariate logistic regression analysis. Sensitivity and specificity of sPD-L1 levels for the detection of ILD in RA patients were 51.7% and 79.3%, respectively (area under the curve = 0.661). Serum sPD-L1 levels were increased in RA patients with ILD. Increased sPD-L1 levels were associated with the presence of ILD.

Wu X ，Xu L ，Cheng Q ，Nie L ，Zhang S ，Du Y ，Xue J ... -  《-》

Identification of Subclinical Lung Involvement in ACPA-Positive Subjects through Functional Assessment and Serum Biomarkers.

Lucchino B ，Di Paolo M ，Gioia C ，Vomero M ，Diacinti D ，Mollica C ，Alessandri C ，Diacinti D ，Palange P ，Di Franco M ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

The serum level and significance of lysyl oxidase-like 2 in patients with rheumatoid arthritis-associated interstitial lung disease.

Fu Q ，Bai Y ，Liu Y ，Zhou J ，Zheng Y ... -  《-》

High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1-6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.

Tyker A ，Ventura IB ，Lee CT ，Strykowski R ，Garcia N ，Guzy R ，Jablonski R ，Vij R ，Strek ME ，Chung JH ，Adegunsoye A ... -  《Scientific Reports》