title: Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options.
abstract: Interferon alpha and its surrogates, including IP-10 and SIGLEC1, paralleled changes of disease activity in systemic lupus erythematosus (SLE). However, the whole blood interferon signature (WBIFNS)-the current standard for type I IFN assessment in SLE-does not correlate with SLE disease activity in individual patients over time. The underlying causes for this apparent contradiction have not been convincingly demonstrated. Using a multicenter dataset of gene expression data from leukocyte subsets in SLE, we identify distinctive subset-specific contributions to the WBIFNS. In a subsequent analysis, the effects of type I interferon on cellular blood composition in patients with SLE and hepatitis B were also studied over time. We found that type I interferon mediates significant alterations in whole blood composition, including a neutropenia and relative lymphocytosis. Given different effects of type 1 interferon on different leukocyte subsets, these shifts confound measurement of a type 1 interferon signature in whole blood. To minimize and overcome these limitations of the WBIFNS, we suggest to measure IFN-induced transcripts or proteins in a specific leukocyte subset to improve clinical impact of interferon biomarkers.
  
  
  
  Myeloid cells contribute more to the WBIFNS in SLE than their lymphocytic counterpart. Very similar leukocyte subsets reveal distinctive IFN signatures. IFN alpha mixes up composition of blood and leads to a preferential neutropenia, yielding relative lymphocytosis.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Strauß
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rose
authors.affiliation: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Flint
authors.affiliation: German Rheumatism Research Center Berlin-Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Klotsche
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.affiliation: Department of Gastroenterology and Hepatology, Medical University Vienna, 1090, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Kyogoku
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Flechsig
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Becker
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Dao
authors.affiliation: German Rheumatism Research Center Berlin-Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Davis
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.affiliation: German Rheumatism Research Center Berlin-Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany. robert.biesen@charite.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Biesen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006526:Hepatitis C / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000032:analysis / Q000097:blood / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008218:Lymphocytosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D007370:Interferon Type I
keywords: Biomarker; Disease activity; Systemic lupus erythematosus; Type I interferon