{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:07:38Z","timestamp":1788361658292,"version":"build-2803163510"},"reference-count":50,"publisher":"The Journal of Rheumatology","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56<jats:sup>dim<\/jats:sup>and CD56<jats:sup>bright<\/jats:sup>NK cells in the early stages of RA development were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Whole blood samples from newly diagnosed, treatment-naive, seropositive (SP) and seronegative (SN) patients with RA (SP RA, n = 45 and SN RA, n = 12), patients with SP arthralgia (n = 30), and healthy controls (HC, n = 41) were assessed for numbers and frequencies of T cells, B cells, and NK cells. SP status was defined as positive for anticyclic citrullinated peptide antibodies (anti-CCP) and\/or rheumatoid factor (RF). Peripheral blood mononuclear cells were used for further analysis of NK cell phenotype and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Total NK cell numbers were decreased in SP RA and SP arthralgia but not in SN RA. Also, NK cells from SP RA showed a decreased potency for interferon-\u03b3 (IFN-\u03b3) production. A selective decrease of CD56<jats:sup>dim<\/jats:sup>, but not CD56<jats:sup>bright<\/jats:sup>, NK cells in SP RA and SP arthralgia was observed. This prompted investigation of CD16 (Fc\u03b3RIIIa) triggering in NK cell apoptosis and cytokine expression.<jats:italic>In vitro,<\/jats:italic>CD16 triggering induced apoptosis of CD56<jats:sup>dim<\/jats:sup>but not CD56<jats:sup>bright<\/jats:sup>NK cells from HC. This apoptosis was augmented by adding interleukin 2 (IL-2). Also, CD16 triggering in the presence of IL-2 stimulated IFN-\u03b3 and tumor necrosis factor-\u03b1 expression by CD56<jats:sup>dim<\/jats:sup>NK cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>The decline of CD56<jats:sup>dim<\/jats:sup>NK cells in SP arthralgia and SP RA and the<jats:italic>in vitro<\/jats:italic>apoptosis of CD56<jats:sup>dim<\/jats:sup>NK cells upon CD16 triggering suggest a functional role of immunoglobulin G-containing autoantibody (anti-CCP and\/or RF)-immune complexes in this process. Moreover, CD16-triggered cytokine production by CD56<jats:sup>dim<\/jats:sup>NK cells may contribute to systemic inflammation as seen in SP arthralgia and SP RA.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.150644","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T01:44:54Z","timestamp":1459561494000},"page":"1008-1016","source":"Crossref","is-referenced-by-count":50,"title":["Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthritis Are Associated with Autoantibody Status"],"prefix":"10.3899","volume":"43","author":[{"given":"Paulina","family":"Chalan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bijzet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart-Jan","family":"Kroesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke 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