Abstract
Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10−11 and 7.09 × 10−6, respectively), and glycerol was higher (Q = 1.20 × 10−6), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780).Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting synovial joints, but extra-articular manifestations are observed
RA patients were diagnosed with usual interstitial pneumonia (UIP); irregular linear opacities and honeycombing, non-specific interstitial pneumonia (NSIP); bilateral ground-glass attenuation patterns predominantly in subpleural and basal regions or no chronic lung diseases (CLDs); and no abnormalities in computed tomography (CT) images, as previously described [11]
The levels of rheumatoid factor, Krebs von den lungen-6 (KL-6), and surfactant protein-D (SP-D) in interstitial lung disease (ILD)(+)RA were higher than those in CLD(–)RA (Table 1), CLD(–) RA was matched for age group, sex, and the use of corticosteroids, csDMARDs, or b/tsDMARDs
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting synovial joints, but extra-articular manifestations are observed. These include interstitial lung disease (ILD), characterized by interstitial inflammation of the lung, in 10.7% of patients [1]. ILD predicts a poor prognosis in RA [2]. Krebs von den lungen-6 (KL-6) and surfactant protein-D (SP-D) have been used as biomarkers for ILD. Their cutoff levels were higher for their application to RA-associated ILD (RA-ILD), and their sensitivity is insufficient [3]. Biomarkers for ILD in RA patients are needed
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