title: Activity of JAK/STAT and NF-kB in patients with axial spondyloarthritis.
abstract: BACKGROUND
  The etiology of axial spondyloarthritis (axSpA) is not fully elucidated. Research continues in determining the mechanisms responsible for initiation of the disease process, its maintenance and development.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the expression of transcription factors STAT (signal transducer and activator of transcription) and NF-κB (nuclear factor kappa B) as well as Janus kinase3 (JAK3) in the peripheral blood leukocytes. We also analyzed the connection between the degree of activation of transcription factors and the disease activity.
  
  
  METHODS
  The study involved 46 patients with axSpA and 19 healthy individuals who comprised the control group. The expression of NF-κB, STAT1, STAT3, STAT4, STAT5, STAT6, and JAK3 in peripheral blood leukocytes was assessed. To determine the degree of activation of transcription factors STAT-s and NF-κB and JAK3 kinase, the immunocytochemistry method was used. For location of the factors, the primary monoclonal anti-NF-κB, anti-JAK3 and polyclonal anti-STAT-s antibodies were used (Chemicon International, USA, Abcam, Cambridge, UK), and the set of antibodies Novocastain Super ABC Kit (Novocastra, UK).
  
  
  RESULTS
  Expression of STAT1, STAT3, STAT4, STAT5, STAT6, NF-κB and JAK3 was statistically higher in the group of patients with axSpA than in the control group. There was a positive correlation with ESR values and expression of STAT4. There was no correlation between STAT, NF-κB, and JAK3 expression and ASDAS, BASDAI, and BASFI. Nine patients were treated with TNF-α inhibitors. The expression of NF-κB and STAT6 was higher in the group treated with TNF-α inhibitors, even though disease activity in these patients was shown to be lower than in those not receiving such treatment (ASDAS = 1.34±0.51 vs. 3.52±0.90, BASDAI = 2.34±1.92 vs. 5.51±2.41).
  
  
  CONCLUSIONS
  In the group of patients with axSpA compared with the control group, higher expression of the transcription factors STAT and NF-κB as well as JAK3 was observed. Due to its crucial roles in inflammation and autoimmunity, STAT4 may have promise as an effective therapeutic target for axSpA.
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Świerkot
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University.
authors.forename: Renata
authors.initials: R
authors.lastname: Sokolik
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences.
authors.forename: Anna
authors.initials: A
authors.lastname: Czarny
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zaczyńska
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Wroclaw.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowak
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw University Hospital.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Chlebicki
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Korman
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University.
authors.forename: Marta
authors.initials: M
authors.lastname: Madej
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw University Hospital.
authors.forename: Patryk
authors.initials: P
authors.lastname: Wojtala
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw University Hospital.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Lubiński
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053616:Janus Kinase 3 / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D050791:STAT Transcription Factors / Q000235:genetics*; D025241:Spondylarthritis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D050791:STAT Transcription Factors; C507933:JAK3 protein, human; D053616:Janus Kinase 3