Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease

Thomas J. Richards, Aaron Eggebeen, Kevin Gibson, Samuel Yousem, Carl Fuhrman, Bernadette R. Gochuico, Noreen Fertig, Chester V. Oddis, Naftali Kaminski, Ivan O. Rosas, Dana P. Ascherman

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Objective. Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. Methods. A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 antibody-positive ILD. Results. Among the 90 anti-Jo-1 antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion. In this large cohort of anti-Jo-1 antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated diseasespecific associations between anti-Jo-1 antibody-positive ILD and serum levels of CRP as well as the interferon-γ-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.

Original languageEnglish (US)
Pages (from-to)2183-2192
Number of pages10
JournalArthritis and Rheumatism
Volume60
Issue number7
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Richards, T. J., Eggebeen, A., Gibson, K., Yousem, S., Fuhrman, C., Gochuico, B. R., Fertig, N., Oddis, C. V., Kaminski, N., Rosas, I. O., & Ascherman, D. P. (2009). Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis and Rheumatism, 60(7), 2183-2192. https://doi.org/10.1002/art.24631