Abstract
BackgroundInterstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases.MethodsA solid-phase antibody array was used for screening 274 biomarkers in pooled sera from collagen disease patients in the AoDILD state and in the stable state. Biomarkers in individual sera were detected without pooling by bead-based immunoassay.ResultsThe serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, interleukin (IL)-2 receptor α (IL-2Rα), and IL-1 receptor antagonist were significantly increased in AoDILD, but TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state. This tendency was also observed in RA patients with AoDILD. Moreover, serum IL-6 level was significantly increased in the AoDILD state in patients with acute exacerbation of ILD (AE-ILD). Serum TIMP-1 and IL-2Rα levels were significantly increased in the AoDILD state in patients with drug-induced ILD (DI-ILD), whereas TIMP-2, MMP-3, and eotaxin 2 levels were decreased. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients with DI-ILD. The serum TIMP-3, MMP-9, osteopontin, IL-2Rα, MMP-1, and MMP-8 levels were significantly increased in the AoDILD state in patients who subsequently died, whereas TIMP-2 and MMP-3 levels were decreased in those who survived. The MMP-3 to MMP-1 ratio was reduced in AoDILD state in patients who died, but not in those who survived.ConclusionsSerum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.
Highlights
Interstitial lung disease (ILD) is frequently associated with collagen diseases
acute-onset diffuse ILD (AoDILD) was classified to acute exacerbation of ILD (AE-ILD), drug-induced ILD (DI-ILD), and Pneumocystis pneumonia as following: Pneumocystis pneumonia was defined by the presence of P. jirovecii organisms detected by polymerase chain reaction for P. jirovecii or Grocott stain from bronchoalveolar lavage fluids or sputa of patients, DI-ILD was defined as AoDILD with treatment of DI-ILD causing drugs at onset after the exclusion of Pneumocystis pneumonia, AEILD was defined as AoDILD without treatment of DI-ILD causing drugs at onset, but with underlying collagen vascular disease-associated ILD (CVD-ILD), after the exclusion of Pneumocystis pneumonia and DI-ILD
Serum tissue inhibitor of metalloproteinase (TIMP)-1, osteopontin, IL-1 receptor antagonist (IL-1RA), IL2Rα, IL-6, and matrix metalloproteinase (MMP)-1 levels were significantly increased in the AoDILD state (Table 1, Figure 1A), whereas TIMP2, MMP-3, and eotaxin 2 levels were decreased
Summary
Interstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. We investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases. Interstitial lung disease (ILD) is characterized by interstitial inflammation of the lung and is frequently associated with collagen diseases, when it is designated collagen vascular disease-associated ILD (CVD-ILD). CVD-ILD is one of the major manifestations of collagen disease that influence the prognosis [1,2]. Acute-onset diffuse ILD (AoDILD) occurs in patients with collagen disease with. Few studies have focused on AoDILD in collagen diseases. We investigated the serum biomarker profile of AoDILD in collagen diseases in order to shed light on pathogenesis and markers informative for disease severity or predicting outcome
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