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

Arthritis Rheum. 2009 Jul;60(7):2183-92. doi: 10.1002/art.24631.

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 disease-specific associations between anti-Jo-1 antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Antinuclear / blood*
  • Antibodies, Antinuclear / immunology
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Chemokine CXCL10 / blood
  • Chemokine CXCL9 / blood
  • Diagnosis, Differential
  • Humans
  • Lung Diseases, Interstitial / blood*
  • Lung Diseases, Interstitial / diagnosis*
  • Lung Diseases, Interstitial / immunology
  • Myositis / blood
  • Myositis / diagnosis
  • Myositis / immunology
  • Polymyositis / blood
  • Polymyositis / diagnosis
  • Polymyositis / immunology
  • Retrospective Studies
  • Sensitivity and Specificity
  • Signal Recognition Particle / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Antinuclear
  • Biomarkers
  • CXCL10 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Jo-1 antibody
  • Signal Recognition Particle
  • C-Reactive Protein