title: IL-17-producing CD4+ T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities.
abstract: OBJECTIVE
  Increased numbers of IL-17-producing CD4(+) T cells have been observed in AS. However, it is not known whether these CD4(+) T cells are already present in early disease or if this is a late disease phenomenon only. Therefore we aimed to investigate whether IL-17-producing CD4(+) T cells are involved in early active axial SpA, including patients without imaging abnormalities, by determining the frequency and phenotype of IL-17-producing CD4(+) T cells in these patients.
  
  
  METHODS
  Flow cytometry was used to analyse cytokine production and surface marker expression of peripheral blood mononuclear cells from 31 patients suffering from early active HLA-B27-positive axial SpA fulfilling the Assessment of SpondyloArthritis International Society criteria with or without MRI abnormalities and 21 healthy controls.
  
  
  RESULTS
  Patients with early active axial SpA showed an increased percentage of IL-17-producing CD4(+) T cells compared with healthy controls (mean 1.1% vs 0.4%, respectively; P = 0.013). The percentage of IL-17-producing CD4(+) T cells was equally increased in patients with and without MRI abnormalities (1.2% vs 1.1%, respectively; P = 0.81). These IL-17-producing CD4(+)T cells expressed the αβ T cell receptor but not the γδ T cell receptor, exhibited a memory phenotype and expressed CD161, but only sporadically expressed killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2).
  
  
  CONCLUSIONS
  IL-17-producing CD4(+) T cells are increased in patients with early active axial SpA both with and without MRI abnormalities. This finding shows that the frequency of IL-17-producing CD4(+) T cells is enhanced in the early stages of disease.
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Diahann T S L
authors.initials: DT
authors.lastname: Jansen
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Hameetman
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergen
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. f.a.van_gaalen@lumc.nl.
authors.forename: Floris A
authors.initials: FA
authors.lastname: van Gaalen
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054347:Receptors, KIR3DL2 / Q000276:immunology; D058566:Sacroiliitis / Q000276:immunology* / Q000473:pathology; D013131:Spine / Q000473:pathology*; D025241:Spondylarthritis / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D020381:Interleukin-17; C515084:KIR3DL2 protein, human; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell; D054347:Receptors, KIR3DL2
keywords: CD4+ T cells; IL-17; KIR; ankylosing spondylitis; axial spondyloarthritis