Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease

Abstract

Background: 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. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases.

Methods: A 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.

Results: The 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.

Conclusions: Serum biomarker profiles could represent prognosis markers for AoDILD in collagen diseases.

Figure 1

Biomarker profile of acute-onset diffuse interstitial lung disease (AoDILD). Increased and decreased biomarkers in AoDILD state of collagen disease and rheumatoid arthritis (RA) patients were indicated in A. Increased and decreased biomarkers in AoDILD state of acute exacerbation of ILD (AE-ILD) and drug-induced interstitial lung disease (DI-ILD) patients were indicated in B. Increased and decreased biomarkers in AoDILD state of patients who subsequently died and those who survived were indicated in C.