RT Journal Article SR Electronic T1 Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthritis Are Associated with Autoantibody Status JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 1008 OP 1016 DO 10.3899/jrheum.150644 VO 43 IS 6 A1 Paulina Chalan A1 Johan Bijzet A1 Bart-Jan Kroesen A1 Annemieke M.H. Boots A1 Elisabeth Brouwer YR 2016 UL http://www.jrheum.org/content/43/6/1008.abstract AB Objective. The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56dim and CD56bright NK cells in the early stages of RA development were studied.Methods. 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.Results. 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-γ (IFN-γ) production. A selective decrease of CD56dim, but not CD56bright, NK cells in SP RA and SP arthralgia was observed. This prompted investigation of CD16 (FcγRIIIa) triggering in NK cell apoptosis and cytokine expression. In vitro, CD16 triggering induced apoptosis of CD56dim but not CD56bright 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-γ and tumor necrosis factor-α expression by CD56dim NK cells.Conclusion. The decline of CD56dim NK cells in SP arthralgia and SP RA and the in vitro apoptosis of CD56dim 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 CD56dim NK cells may contribute to systemic inflammation as seen in SP arthralgia and SP RA.