title: Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.
abstract: OBJECTIVE
  TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.
  
  
  METHODS
  Patients with RA were recruited for this study, (i) RA patients in clinical remission following a minimum of one year of TNFi therapy (n = -15); (2) Active RA patients, not currently or ever receiving TNFi (n = 18); and healthy control volunteers (n = 15). Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b) expression on T-(CD3+CD56-), NK-(CD3-CD56+) and NKT-(CD3+CD56+) cells was determined by flow cytometry.
  
  
  RESULTS
  Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05). CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05), with no differences observed for CD161 and CD57. CD3+CD56- cell expression of NKG2A was inversely related to DAS28 (r = -0.612, p<0.005).
  
  
  CONCLUSIONS
  High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with disease flare following withdrawal of therapy.
authors.affiliation: Translation Rheumatology Research Group, Dublin Academic Medical Centre, St. Vincent's University Hospital, Elm Park, Dublin, Ireland. cearaesmondewalsh@physicians.ie
authors.forename: Ceara E
authors.initials: CE
authors.lastname: Walsh
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ryan
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.forename: Oliver
authors.initials: O
authors.lastname: FitzGerald
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Veale
authors.forename: Barry
authors.initials: B
authors.lastname: Bresnihan
authors.forename: Ursula
authors.initials: U
authors.lastname: Fearon
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D012074:Remission Induction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D014409:Tumor Necrosis Factor-alpha
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