title: Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus.
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.
  
  
  RESULTS
  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.
authors.affiliation: Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bauer
authors.forename: Emily C
authors.initials: EC
authors.lastname: Baechler
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Franak M
authors.initials: FM
authors.lastname: Batliwalla
authors.forename: Dianna
authors.initials: D
authors.lastname: Crawford
authors.forename: Ward A
authors.initials: WA
authors.lastname: Ortmann
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Espe
authors.forename: Wentian
authors.initials: W
authors.lastname: Li
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay; D007370:Interferon Type I / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D018925:Chemokines; D007370:Interferon Type I; D020543:Proteome