title: Interferon-inducible chemokines reflect severity and progression in sarcoidosis.
abstract: BACKGROUND
  Identification of serum proteins that track with disease course in sarcoidosis may have clinical and pathologic importance. We previously identified up-regulated transcripts for interferon-inducible chemokines CXCL9, and CXCL10, in blood of sarcoidosis patients compared to controls. The objective of this study was to determine whether proteins encoded by these transcripts were elevated in serum and identified patients with remitting vs. chronic progressive sarcoidosis longitudinally.
  
  
  METHODS
  Serum levels of CXCL9, CXCL10, and proteins associated with inflammation and/or disease activity (sIL2R, ACE, ESR and CRP) were measured in a prospective cohort of sarcoidosis subjects and controls. Comparisons were made between groups and clinical course using pulmonary function measures and a severity score developed by Wasfi et al.
  
  
  RESULTS
  In a cross-sectional analysis of 36 non-immunosuppressed sarcoidosis subjects, serum CXCL9, CXCL10, and sIL2R were significantly elevated compared to 46 controls (p < 0.0001). CXCL9 and CXCL10 were strongly inter-correlated (p = 0.0009). CXCL10 and CXCL9 were inversely correlated with FVC% predicted and DLCO% predicted, respectively. CXCL10 and CXCL9 significantly correlated with sarcoidosis severity score. sIL2R, ESR, CRP, and ACE serum levels did not correlate with pulmonary function measures or severity score. In the longitudinal analysis of 26 subjects, changes in serum CXCL10 level over time corresponded with progression versus remission of disease.
  
  
  CONCLUSIONS
  Interferon-γ-inducible chemokines, CXCL9 and CXCL10, are elevated in sarcoidosis and inter-correlated with each other. Chemokine levels correlated with measures of disease severity. Serial measurements of CXCL10 corresponded to clinical course.
authors.forename: Robert
authors.initials: R
authors.lastname: Su
authors.forename: Michelle-Linh T
authors.initials: ML
authors.lastname: Nguyen
authors.forename: Misha R
authors.initials: MR
authors.lastname: Agarwal
authors.forename: Christopher
authors.initials: C
authors.lastname: Kirby
authors.forename: Christine P
authors.initials: CP
authors.lastname: Nguyen
authors.forename: Joris
authors.initials: J
authors.lastname: Ramstein
authors.forename: Eli P
authors.initials: EP
authors.lastname: Darnell
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Gomez
authors.forename: Melissa
authors.initials: M
authors.lastname: Ho
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, University of California San Francisco, 505 Parnassus Avenue, Box 0111, San Francisco, CA 94143, USA. laura.koth@ucsf.edu.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Koth
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000097:blood*; D054370:Chemokine CXCL9 / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000097:blood; D017565:Sarcoidosis, Pulmonary / Q000097:blood* / Q000175:diagnosis*; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D015375:Receptors, Interleukin-2; D002097:C-Reactive Protein