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Comparative Profiling of Serum Protein Biomarkers in Rheumatoid Arthritis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
Author(s) -
Kass Daniel J.,
Nouraie Mehdi,
Glassberg Marilyn K.,
Ramreddy Nitya,
Fernandez Karen,
Harlow Lisa,
Zhang Yingze,
Chen Jean,
Kerr Gail S.,
Reimold Andreas M.,
England Bryant R.,
Mikuls Ted R.,
Gibson Kevin F.,
Dellaripa Paul F.,
Rosas Ivan O.,
Oddis Chester V.,
Ascherman Dana P.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41123
Subject(s) - medicine , rheumatoid arthritis , idiopathic pulmonary fibrosis , interstitial lung disease , cohort , immunology , pulmonary fibrosis , lung
Objective Interstitial lung disease ( ILD ) is a frequent complication of rheumatoid arthritis ( RA ), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis–associated ILD ( RA ‐ ILD ) and idiopathic pulmonary fibrosis ( IPF ). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA ‐ ILD and IPF . Methods Multiplex enzyme‐linked immunosorbent assays ( ELISA s) were used to profile 45 protein biomarkers encompassing cytokines/chemokines, growth factors, and matrix metalloproteinases ( MMP s) in sera obtained from RA patients with ILD and those without, individuals with IPF , and healthy controls. Levels of selected serum proteins were compared between patient subgroups using adjusted linear regression, principal component analysis ( PCA ), and least absolute shrinkage and selection operator ( LASSO ) modeling. Results Multiplex ELISA ‐based assessment of sera from 2 independent cohorts (Veterans Affairs [VA] and Non‐ VA ) revealed a number of non‐overlapping biomarkers distinguishing RA ‐ ILD from RA without ILD ( RA –no ILD ) in adjusted regression models. Parallel analysis of sera from IPF patients also yielded a discriminatory panel of protein markers in models adjusted for age/sex/smoking, which showed differential overlap with profiles linked to RA ‐ ILD in the VA cohort versus the Non‐ VA cohort. PCA revealed several distinct functional groups of RA ‐ ILD –associated markers that, in the VA cohort, encompassed proinflammatory cytokines/chemokines as well as 2 different subsets of MMP s. Finally, LASSO regression modeling in the Non‐ VA and VA cohorts revealed distinct biomarker combinations capable of discriminating RA ‐ ILD from RA –no ILD . Conclusion Comparative serum protein biomarker profiling represents a viable method for distinguishing RA ‐ ILD from RA –no ILD and identifying population‐specific mediators shared with IPF .