Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus

Jason W. Bauer, Emily C. Baechler, Michelle Petri, Franak M. Batliwalla, Dianna Crawford, Ward A. Ortmann, Karl J. Espe, Wentian Li, Dhavalkumar D. Patel, Peter K. Gregersen, Timothy W. Behrens

Research output: Contribution to journalArticle

Abstract

Background: Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disorder that affects multiple organ systems and is characterized by unpredictable flares of disease. Recent evidence indicates a role for type I interferon (IFN) in SLE pathogenesis; however, the downstream effects of IFN pathway activation are not well understood. Here we test the hypothesis that type I IFN-regulated proteins are present in the serum of SLE patients and correlate with disease activity. Methods and Findings: We performed a comprehensive survey of the serologic proteome in human SLE and identified dysregulated levels of 30 cytokines, chemokines, growth factors, and soluble receptors. Particularly striking was the highly coordinated up-regulation of 12 inflammatory and/or homeostatic chemokines, molecules that direct the movement of leukocytes in the body. Most of the identified chemokines were inducible by type I IFN, and their levels correlated strongly with clinical and laboratory measures of disease activity. Conclusions: These data suggest that severely disrupted chemokine gradients may contribute to the systemic autoimmunity observed in human SLE. Furthermore, the levels of serum chemokines may serve as convenient biomarkers for disease activity in lupus.

Original languageEnglish (US)
Pages (from-to)2274-2284
Number of pages11
JournalPLoS medicine
Volume3
Issue number12
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Medicine(all)

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    Bauer, J. W., Baechler, E. C., Petri, M., Batliwalla, F. M., Crawford, D., Ortmann, W. A., Espe, K. J., Li, W., Patel, D. D., Gregersen, P. K., & Behrens, T. W. (2006). Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS medicine, 3(12), 2274-2284. https://doi.org/10.1371/journal.pmed.0030491