Blood protein biomarkers for rheumatoid arthritis patients complicated by interstitial lung disease.

OBJECTIVE: The prognosis of patients with rheumatoid arthritis (RA) complicated with interstitial lung disease (ILD) is very poor. We used blood protein profiles to identify biomarkers for ILD in patients with RA. METHODS: Proteome analyses of plasma samples from 16 RA patients with ILD or without chronic lung disease (CLD) were performed with a proteomic assay using antibody immunoassay and next generation sequencing. Validation of the results was achieved by multiplex bead-based immunoassay of 20 candidate protein biomarkers in serum of 96 RA patients with ILD or without CLD. RESULTS: Levels of carbohydrate antigen 125 (CA125), C-X-C motif chemokine ligand (CXCL)9, CXCL13, interleukin (IL)-19, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, and TIMP-4 were increased and those of C-C motif chemokine ligand (CCL)3 were decreased in RA with ILD compared with those without CLD. Multiple logistic regression analysis of CXCL9, CXCL13, and TIMP-1 was performed to generate an ILD-index. The area under the curve value of receiver operating characteristic curve of ILD-index was 0.818 (95% confidence interval 0.730-0.907). CONCLUSIONS: Blood biomarker profiles could represent diagnostic biomarkers for ILD in RA.