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Functionally active NKG2A-expressing natural killer cells are elevated in rheumatoid arthritis patients compared to psoriatic arthritis patients and healthy donors
S.T. Van Bijnen1, M. Cossu2, M.W. Roeven3, T.L. Jansen4, F. Preijers5, J. Spanholtz6, H. Dolstra7, T.R. Radstake8
- Department of Hematology, and Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
- 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.
- Department of Hematology, and Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
- Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
- Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
- Glycostem Therapeutics, Oss, The Netherlands.
- Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
- Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. T.R.D.J.Radstake@umcutrecht.nl
CER8311
2015 Vol.33, N°6
PI 0795, PF 0804
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PMID: 26411696 [PubMed]
Received: 23/01/2015
Accepted : 04/05/2015
In Press: 28/09/2015
Published: 15/12/2015
Abstract
OBJECTIVES:
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.
