title: Biomarkers of rheumatoid arthritis-associated interstitial lung disease.
abstract: OBJECTIVE
  Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.
  
  
  METHODS
  Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest.
  
  
  RESULTS
  MMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.
  
  
  CONCLUSIONS
  Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
authors.affiliation: First Hospital of Xiamen University, Xiamen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Doyle
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Liu
authors.forename: Rohit
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Sheng Xiang
authors.initials: SX
authors.lastname: Ge
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Cai
authors.forename: Diane
authors.initials: D
authors.lastname: Koontz
authors.forename: Carl R
authors.initials: CR
authors.lastname: Fuhrman
authors.forename: Maria F
authors.initials: MF
authors.lastname: Golzarri
authors.forename: Yushi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatabu
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Araki
authors.forename: Paul F
authors.initials: PF
authors.lastname: Dellaripa
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Rosas
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D002681:China; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D014481:United States
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D020783:Matrix Metalloproteinase 7