Biomarkers of rheumatoid arthritis-associated interstitial lung disease

Juan Chen, Tracy J. Doyle, Yongliang Liu, Rohit Aggarwal, Xiaoping Wang, Yonghong Shi, Sheng Xiang Ge, Heqing Huang, Qingyan Lin, Wen Liu, Yongjin Cai, Diane Koontz, Carl R. Fuhrman, Maria F. Golzarri, Yushi Liu, Hiroto Hatabu, Mizuki Nishino, Tetsuro Araki, Paul F. Dellaripa, Chester V. OddisIvan O. Rosas, Dana Ascherman

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Conclusion 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.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalArthritis and Rheumatology
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2015

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Interstitial Lung Diseases
Rheumatoid Arthritis
Biomarkers
Matrix Metalloproteinase 7
Logistic Models
Enzyme-Linked Immunosorbent Assay
Chemokine CXCL10
Acute-Phase Proteins
Matrix Metalloproteinases
Chemokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology

Cite this

Biomarkers of rheumatoid arthritis-associated interstitial lung disease. / Chen, Juan; Doyle, Tracy J.; Liu, Yongliang; Aggarwal, Rohit; Wang, Xiaoping; Shi, Yonghong; Ge, Sheng Xiang; Huang, Heqing; Lin, Qingyan; Liu, Wen; Cai, Yongjin; Koontz, Diane; Fuhrman, Carl R.; Golzarri, Maria F.; Liu, Yushi; Hatabu, Hiroto; Nishino, Mizuki; Araki, Tetsuro; Dellaripa, Paul F.; Oddis, Chester V.; Rosas, Ivan O.; Ascherman, Dana.

In: Arthritis and Rheumatology, Vol. 67, No. 1, 01.01.2015, p. 28-38.

Research output: Contribution to journalArticle

Chen, J, Doyle, TJ, Liu, Y, Aggarwal, R, Wang, X, Shi, Y, Ge, SX, Huang, H, Lin, Q, Liu, W, Cai, Y, Koontz, D, Fuhrman, CR, Golzarri, MF, Liu, Y, Hatabu, H, Nishino, M, Araki, T, Dellaripa, PF, Oddis, CV, Rosas, IO & Ascherman, D 2015, 'Biomarkers of rheumatoid arthritis-associated interstitial lung disease', Arthritis and Rheumatology, vol. 67, no. 1, pp. 28-38. https://doi.org/10.1002/art.38904
Chen, Juan ; Doyle, Tracy J. ; Liu, Yongliang ; Aggarwal, Rohit ; Wang, Xiaoping ; Shi, Yonghong ; Ge, Sheng Xiang ; Huang, Heqing ; Lin, Qingyan ; Liu, Wen ; Cai, Yongjin ; Koontz, Diane ; Fuhrman, Carl R. ; Golzarri, Maria F. ; Liu, Yushi ; Hatabu, Hiroto ; Nishino, Mizuki ; Araki, Tetsuro ; Dellaripa, Paul F. ; Oddis, Chester V. ; Rosas, Ivan O. ; Ascherman, Dana. / Biomarkers of rheumatoid arthritis-associated interstitial lung disease. In: Arthritis and Rheumatology. 2015 ; Vol. 67, No. 1. pp. 28-38.
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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.Conclusion 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.",
author = "Juan Chen and Doyle, {Tracy J.} and Yongliang Liu and Rohit Aggarwal and Xiaoping Wang and Yonghong Shi and Ge, {Sheng Xiang} and Heqing Huang and Qingyan Lin and Wen Liu and Yongjin Cai and Diane Koontz and Fuhrman, {Carl R.} and Golzarri, {Maria F.} and Yushi Liu and Hiroto Hatabu and Mizuki Nishino and Tetsuro Araki and Dellaripa, {Paul F.} and Oddis, {Chester V.} and Rosas, {Ivan O.} and Dana Ascherman",
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T1 - Biomarkers of rheumatoid arthritis-associated interstitial lung disease

AU - Chen, Juan

AU - Doyle, Tracy J.

AU - Liu, Yongliang

AU - Aggarwal, Rohit

AU - Wang, Xiaoping

AU - Shi, Yonghong

AU - Ge, Sheng Xiang

AU - Huang, Heqing

AU - Lin, Qingyan

AU - Liu, Wen

AU - Cai, Yongjin

AU - Koontz, Diane

AU - Fuhrman, Carl R.

AU - Golzarri, Maria F.

AU - Liu, Yushi

AU - Hatabu, Hiroto

AU - Nishino, Mizuki

AU - Araki, Tetsuro

AU - Dellaripa, Paul F.

AU - Oddis, Chester V.

AU - Rosas, Ivan O.

AU - Ascherman, Dana

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.Conclusion 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.

AB - 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.Conclusion 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.

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