title: MxA as a clinically applicable biomarker for identifying systemic interferon type I in primary Sjogren's syndrome.
abstract: OBJECTIVE
  To establish an easy and practical assay for identifying systemic interferon (IFN) type I bioactivity in patients with primary Sjögren's syndrome (pSS). The IFN type I signature is present in over half of the pSS patients and identifies a subgroup with a higher disease activity. This signature is currently assessed via laborious expression profiles of multiple IFN type I-inducible genes.
  
  
  METHODS
  In a cohort of 35 pSS patients, myxovirus-resistance protein A (MxA) was assessed as a potential biomarker for type I IFN activity, using an enzyme immunoassay (EIA) on whole-blood and flow cytometric analyses (fluorescence-activated cell sorting, FACS) of isolated CD14 monocytes. In addition, potential biomarkers such as CD64, CD169 and B cell-activating factor (BAFF) were simultaneously analysed in CD14 monocytes using FACS. The IFNscore, a measure for total type I IFN bioactivity, was calculated using expression values of the IFN type I signature genes--IFI44, IFI44L, IFIT3, LY6E and MX1--in CD14 monocytes, determined by real-time quantitative PCR.
  
  
  RESULTS
  IFNscores correlated the strongest with monocyte MxA protein (r=0.741, p<0.001) and whole-blood MxA levels (r=0.764, p<0.001), weaker with CD169 (r=0.495, p<0.001) and CD64 (r=0.436, p=0.007), and not at all with BAFF protein. In particular, whole blood MxA levels correlated with EULAR Sjögren's Syndrome Disease Activity Index scores and numerous clinical pSS parameters. Interestingly, patients on hydroxychloroquine showed reduced MxA levels (EIA, p=0.04; FACS p=0.001).
  
  
  CONCLUSIONS
  The MxA assays were excellent tools to assess IFN type I activity in pSS, MxA-EIA being the most practical. MxA levels associate with features of active disease and are reduced in hydroxychloroquine-treated patients, suggesting the clinical applicability of MxA in stratifying patients according to IFN positivity.
authors.affiliation: Department of Immunology, Erasmus MC, , Rotterdam, Zuid-holland, The Netherlands.
authors.forename: Naomi I
authors.initials: NI
authors.lastname: Maria
authors.forename: Zana
authors.initials: Z
authors.lastname: Brkic
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: van Helden-Meeuwsen
authors.forename: Kim
authors.initials: K
authors.lastname: Heezen
authors.forename: Joop P
authors.initials: JP
authors.lastname: van de Merwe
authors.forename: Paul L
authors.initials: PL
authors.lastname: van Daele
authors.forename: Virgil A S H
authors.initials: VA
authors.lastname: Dalm
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Versnel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D000954:Antigens, Surface; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D058851:GPI-Linked Proteins; C065888:IFI44 protein, human; C116468:IFIT3 protein, human; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; C439870:LY6E protein, human; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger
keywords: Disease Activity; Sjøgren's Syndrome; Treatment