title: Functionally active NKG2A-expressing natural killer cells are elevated in rheumatoid arthritis patients compared to psoriatic arthritis patients and healthy donors.
abstract: OBJECTIVE
  Natural killer cell receptors (NKR) have been implicated in rheumatoid (RA) and psoriatic arthritis (PsA) pathogenesis. To gain more insight into their role, we characterised NKR (co-)expression patterns on NK and T cells and NK cell function in RA and PsA.
  
  
  METHODS
  The frequency of NK and T cells expressing killer like immunoglobulin (KIR) and NKG2 receptors and natural cytotoxicity receptors was assessed by 10-colour flow cytometry in peripheral blood of 23 RA, 12 PsA patients and 18 healthy donors (HD). NK cell cytotoxicity and IFN-gamma production was assessed in 8 RA patients and 8 HD.
  
  
  RESULTS
  In RA but not PsA, the frequency of NK cells (median; range) expressing NKG2A (42%; 14-81%) was elevated compared to HD (23%; 9-58%). NKG2A⁺ NK cells predominantly lack KIR, but display normal cytotoxicity and IFN-γ production. In contrast, RA patients with normal NKG2A⁺ NK cell frequency have less functional NK cells compared to HD. T cells expressing Fc-gamma receptor CD16 were elevated in RA (median 0.75%) versus HD (0.3%). Furthermore, T cells expressing the KIRs CD158ah in both RA (0.7%) and PsA (0.3%), and CD158e1e2 in RA (1.5%) were elevated compared to HD (0.2% and 0.4%, respectively). In RA, CD4⁺ T cells expressing the KIRs CD158ah, CD158b1b2j and CD158e1e2 were low (<2%) but significantly elevated compared to HD.
  
  
  CONCLUSIONS
  This study demonstrates the presence of an elevated, functionally active NKG2A⁺ KIR- NK cell population in RA. Together with an elevated frequency of NKR-expressing T cells, these changes may reflect differential pathogenetic involvement.
authors.affiliation: Department of Hematology, and Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: S T A
authors.initials: ST
authors.lastname: van Bijnen
authors.affiliation: Dept.of Rheumatology, Clinical Immunology and Lab. of Translational Immunology, University Medical Center Utrecht, The Netherlands; and Referral Center for Systemic Autoimmune Dis., Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cossu
authors.affiliation: Department of Hematology, and Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M W H
authors.initials: MW
authors.lastname: Roeven
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: T L
authors.initials: TL
authors.lastname: Jansen
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Preijers
authors.affiliation: Glycostem Therapeutics, Oss, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Spanholtz
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Dolstra
authors.affiliation: Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. T.R.D.J.Radstake@umcutrecht.nl.
authors.forename: T R D J
authors.initials: TR
authors.lastname: Radstake
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology*; D054340:Receptors, KIR / Q000276:immunology; D055636:Receptors, Natural Cytotoxicity Triggering / Q000276:immunology
chemical_list: C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR; D055636:Receptors, Natural Cytotoxicity Triggering