THU0083 THE DISPROPORTION OF NK CELLS AND NON-CONVENTIONAL NK-T CELLS AND ΓΔ-T CELLS IN INDIVIDUALS AT RISK OF DEVELOPING RHEUMATOID ARTHRITIS. (13th June 2020) - Prajzlerová, K.
Abstract : Background: Natural killer (NK) cells and non-conventional T cells (NK-T and γδ-T cells) are involved in the regulation of immune system and their alteration was previously described in patients with established rheumatoid arthritis (RA). The positivity of antibodies against citrullinated proteins (ACPA) significantly increases the risk of progression to RA. The clinical characteristics of individuals at risk of progression to RA (clinically suspect arthralgia, CSA) has recently been established by EULAR irrespective of the ACPA status. Objectives: We aimed to study lymphocyte subpopulations in individuals at risk of developing RA. Methods: Our study included 95 individuals with arthralgia at risk of developing RA based on ACPA positivity and/or meeting CSA definition and 70 age and gender matched healthy controls (HC). Whole blood samples were analysed by flow cytometry. The percentage and absolute count of CD3+ T cells, CD3-CD16/56+ NK cells, CD3+CD16/56+ NK-T cells and CD3bright γδ-T cells were evaluated in CD45+CD14- lymphocyte populations. Results: Out of 95 individuals with arthralgia (median age 47 years [IQR=16], 92% females), 58 were ACPA+ and 62 met CSA definition (26 of them were ACPA+). Median symptom duration was 12 months [IQR=53], CRP 2.43 [IQR=3.32]. As per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Fourteen individuals developed RA within a median of 3 months of follow up with CRP 4.34 [IQR=17.46] and DAS28(CRP) score 4.84 [IQR=2.43]. Analysis of lymphocyte subpopulations showed higher %CD3+ T cells (p=0.001) and lower %NK (p=0.002) as well as absolute count of NK (p≤0.001), NK-T (p=0.016) and γδ-T cells (p=0.025) and trend to lower %NK-T (p=0.054) in all individuals with arthralgia compared to HC. Similarly, higher %CD3+ T cells (p=0.005) and lower %NK (p=0.004), %NK-T (p=0.027), %γδ-T cells (p=0.050) and absolute count of NK (p=0.002), NK-T (p=0.016) and γδ-T cells (p=0.019) were confirmed in a subgroup of ACPA+ individuals compared to HC. In addition, individuals who met CSA criteria irrespective of ACPA status had higher %CD3 T cells (p=0.004) and lower %NK cells (p=0.002) and absolute count of NK (p≤0.001), NK-T (p=0.019) and γδ-T cells (p=0.042) compared to HC. We observed no differences either between ACPA- or CSA- and HC or between ACPA+ and ACPA- or CSA+ and CSA- individuals with arthralgia. In addition, there were no differences in lymphocyte subsets in individuals who have developed RA so far and patients with arthralgia or at the time of RA manifestation. Conclusion: We identified lower number of NK cells as well as NK-T and γδ-T cells in individuals at risk of developing of RA. The decrease in non-conventional T cells was observed despite the increased percentage of the classical T cells. We hypothesize that the disproportion of these lymphocyte subpopulations, described previously in established RA, observed here in at-risk individuals may reflect their predisposition for further development of RA. Acknowledgments: Projects AZV-17-32612A and MHCR 023728 Disclosure of Interests: Klára Prajzlerová: None declared, Olga Kryštůfková: None declared, Nora Petrovská: None declared, Petra Hánová: None declared, Hana Hulejova: None declared, Monika Gregová Consultant of: Novartis, Abbvie, Paid instructor for: Novartis, Speakers bureau: Novartis, Abbvie, MSD, Heřman Mann: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Mária Filková: None declared