title: Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases.
abstract: OBJECTIVE
  Type 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1-associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis.
  
  
  METHODS
  CD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed.
  
  
  RESULTS
  1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN-1-associated genes in T cells was restricted to SLE.
  
  
  CONCLUSIONS
  Given the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE.
authors.affiliation: Department of Medicine, The University of Cambridge, Cambridge, UK; Cambridge Institute of Medical Research, The University of Cambridge, Cambridge, UK.
authors.forename: Shaun M
authors.identifier: 0000-0002-5282-9334
authors.initials: SM
authors.lastname: Flint
authors.affiliation: Immunology Programme and Department of Microbiology Centre for Life Sciences , National University of Singapore , Singapore , Singapore.
authors.forename: Vojislav
authors.initials: V
authors.lastname: Jovanovic
authors.affiliation: Department of Medicine , Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore.
authors.forename: Boon Wee
authors.initials: BW
authors.lastname: Teo
authors.affiliation: Department of Medicine , Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore.
authors.forename: Anselm
authors.initials: A
authors.lastname: Mak
authors.affiliation: Department of Rheumatology and Immunology , Singapore General Hospital , Singapore , Singapore.
authors.forename: Julian
authors.initials: J
authors.lastname: Thumboo
authors.affiliation: Department of Medicine, The University of Cambridge, Cambridge, UK; Cambridge Institute of Medical Research, The University of Cambridge, Cambridge, UK.
authors.forename: Eoin F
authors.initials: EF
authors.lastname: McKinney
authors.affiliation: Department of Medicine, The University of Cambridge, Cambridge, UK; Cambridge Institute of Medical Research, The University of Cambridge, Cambridge, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Immunology Programme and Department of Microbiology Centre for Life Sciences , National University of Singapore , Singapore , Singapore.
authors.forename: Paul
authors.initials: P
authors.lastname: MacAry
authors.affiliation: Immunology Programme and Department of Microbiology Centre for Life Sciences , National University of Singapore , Singapore , Singapore.
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
authors.affiliation: Department of Medicine , The University of Cambridge , Cambridge , UK.
authors.forename: David Rw
authors.initials: DR
authors.lastname: Jayne
authors.affiliation: Department of Rheumatology and Immunology , Singapore General Hospital , Singapore , Singapore.
authors.forename: Kok Yong
authors.initials: KY
authors.lastname: Fong
authors.affiliation: Department of Medicine, The University of Cambridge, Cambridge, UK; Cambridge Institute of Medical Research, The University of Cambridge, Cambridge, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.affiliation: Department of Medicine, The University of Cambridge, Cambridge, UK; Cambridge Institute of Medical Research, The University of Cambridge, Cambridge, UK; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Kenneth Gc
authors.initials: KG
authors.lastname: Smith
keywords: Autoimmunity; Cytokines; Systemic Lupus Erythematosus