title: Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus.
abstract: BACKGROUND
  More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy.
  
  
  METHODS
  Monocyte surface expression of Fcgamma receptors (FcgammaRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcgammaR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR.
  
  
  RESULTS
  Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcgammaRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy.
  
  
  CONCLUSIONS
  Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients.
authors.affiliation: Division of Rheumatology & Clinical Immunology, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610-0221, USA. liyi@medicine.ufl.edu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Erinn S
authors.initials: ES
authors.lastname: Kellner
authors.forename: Matthew
authors.initials: M
authors.lastname: Paulus
authors.forename: Juliana
authors.initials: J
authors.lastname: Switanek
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zhuang
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000941:Antigens / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008297:Male; D064547:Myxovirus Resistance Proteins; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D000941:Antigens; D000954:Antigens, Surface; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D058851:GPI-Linked Proteins; C065888:IFI44 protein, human; D007370:Interferon Type I; C439870:LY6E protein, human; D064547:Myxovirus Resistance Proteins; D017452:Receptors, IgG; D019204:GTP-Binding Proteins