title: Plasma levels of galectin-3-binding protein reflect type I interferon activity and are increased in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Simple measures of type I interferon (IFN) activity constitute highly attractive biomarkers in systemic lupus erythematosus (SLE). We explore galectin-3-binding protein (G3BP) as a novel measure of type I IFN activity and serum/plasma biomarker in large independent cohorts of patients with SLE and controls.
  
  
  METHODS
  Serum and plasma G3BP concentrations were quantified using ELISA. Type I IFN activity was assessed by Mx1 reporter gene expression assays and correlated to serum G3BP concentrations (SLE-IFN-α, n=26 and healthy controls (HCs), n=10). Plasma G3BP concentrations in the SLE-Denmark (DK) (n=70) and SLE-Sweden (SE) (n=68) cohorts were compared with the HC-DK (n=47) and HC-SE (n=50) cohorts and patients with systemic sclerosis (n=111). In 15 patients with SLE, serum G3BP in consecutive samples was correlated to disease activity. Correlation analysis between G3BP, clinical parameters including disease activity in the four SLE cohorts was performed.
  
  
  RESULTS
  G3BP concentrations correlated significantly with the IFN-α reporter gene assay (r=0.56, p=0.0005) and with IFN-α gene expression scores (r=0.54, p=0.0002). Plasma concentrations were significantly increased in the SLE-DK and SLE-SE cohorts compared with HCs and patients with systemic sclerosis (p<0.0001 and p=0.0009). G3BP concentrations correlated with disease activity measures in the SLE-DK- and SLE-IFN-α cohorts (p=0.0004 and p=0.05) but not in the SLE-SE cohort (p=0.98). Markedly temporal variation was observed in G3BP levels in the consecutive SLE-samples and was significantly associated with changes in disease activity (r=0.44, p=0.014).
  
  
  CONCLUSIONS
  G3BP plasma levels reflect type I IFN activity and are increased in SLE. Associations with disease activity or clinical manifestations are uncertain. This study highlights G3BP as a convenient measure of type I IFN-dependent gene activation.
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics , Statens Serum Institut , Copenhagen , Denmark ; Department of Infectious Diseases & Rheumatology , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Christoffer T
authors.initials: CT
authors.lastname: Nielsen
authors.affiliation: Department of Rheumatology , Skåne University Hospital and Lund University , Lund , Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Lood
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics , Statens Serum Institut , Copenhagen , Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Ostergaard
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics , Statens Serum Institut , Copenhagen , Denmark ; Department of Dermatology, Bispebjerg , Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Line V
authors.initials: LV
authors.lastname: Iversen
authors.affiliation: Department of Rheumatology , Odense University Hospital , Odense , Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Voss
authors.affiliation: Department of Rheumatology , Skåne University Hospital and Lund University , Lund , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bengtsson
authors.affiliation: Department of Infectious Diseases & Rheumatology , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics , Statens Serum Institut , Copenhagen , Denmark.
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
keywords: Autoantibodies; Interferon; Lupus Nephritis; Systemic Lupus Erythematosus; Systemic Sclerosis