Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus.
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.
Bauer
Jason W
JW
Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Baechler
Emily C
EC
Petri
Michelle
M
Batliwalla
Franak M
FM
Crawford
Dianna
D
Ortmann
Ward A
WA
Espe
Karl J
KJ
Li
Wentian
W
Patel
Dhavalkumar D
DD
Gregersen
Peter K
PK
Behrens
Timothy W
TW
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
D015415:Biomarkers; D018925:Chemokines; D007370:Interferon Type I; D020543:Proteome