THU0062\u2005THE DYSREGULATION OF NK CELLS AND NON-CLASSICAL AND CLASSICAL MONOCYTE SUBPOPULATIONS IN INDIVIDUALS AT RISK OF DEVELOPING RHEUMATOID ARTHRITIS

Abstract

Background: Antibodies against citrullinated proteins (ACPA) are present months to years before the clinical manifestation of rheumatoid arthritis (RA). ACPA+ individuals are at 8-10x higher risk of developing RA compared to seronegative individuals. EULAR characterised individuals with arthralgia suspicious for progression to RA based on their clinical features (clinically suspect arthralgia, CSA). Objectives: The alteration of natural killer (NK) cells and monocyte subpopulations in patients with established RA has been previously described. We therefore aimed to study the lymphocyte and monocyte subpopulations in individuals in the preclinical phase of RA. Methods: Our study included 49 individuals with arthralgia (mean age 45.97±11.95 years; 92% females) and 80 age and gender matched healthy controls (HC). Leukocytes from peripheral blood were analysed by flow cytometry. Lymphocyte subpopulations were defined as B (CD19+CD3-), T (CD3+CD4+, CD3+CD8+) and NK (CD16/56+CD3-) cells. Monocytes were further classified to classical (CD14++CD16-), intermediate (CD14++CD16+/++) and non-classical (CD14-/+CD16++) subsets. Data were analysed using Mann Whitney test and expressed as median and interquartile range [IQR]. Results: Out of 49 individuals with arthralgia, 36 were ACPA+ and 28 met CSA definition (15 of them were ACPA+), with symptoms duration 21 months [IQR=53], CRP 3.18 mg/L [IQR=3.6], DAS28 score 2.28 [IQR=1.31]. As per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Ten individuals developed RA within a median of 4 months of follow up. Individuals with arthralgia had higher%CD3+ T cells (78.10 [8.10] vs. 75.04 [9.26], p=0.001) and lower%NK (11.20 [7.20] vs. 12.89 [6.62], p≤0.001) as well as absolute count of NK cells (0.18 [0.13] vs. 0.24 [0.17], p≤0.001) compared to HC. Similarly, higher%CD3+ T cells (77.95 [8.65] vs. 75.04 [9.26], p=0.003) and lower%NK (10.85 [7.81] vs. 12.89 [6.62], p=0.003) and absolute count of NK cells (0.20 [0.14] vs. 0.24 [0.17], p=0.003) was confirmed in a subgroup of ACPA+ individuals compared to HC. Moreover, individuals who developed RA during follow up, had a lower baseline absolute count of NK cells (0.14 [0.10] vs. 0.19 [0.15], p=0.039). Analysis of monocyte subpopulations revealed higher count of non-classical (5.99 [4.87] vs. 4.03; IQR [3.28], p=0.022) and intermediate (5.82 [2.93] vs. 4.31 [2.08], p=0.034) monocytes and lower count of classical monocytes (86.06 [7.69] vs. 89.41 [3.52], p=0.005) in individuals with arthralgia compared to HC. Specifically, also ACPA+ patients had higher count of non-classical (6.07 [5.84 vs. 4.03 [3.28, p=0.020) and intermediate (5.86 [3.05] vs. 4.31 [2.08], p=0.036) and lower count of classical (85.43 [8.34] vs. 89.41 [3.59], p=0.005) monocytes compared to HC. There was no difference in% or absolute count of lymphocytes and monocytes subpopulations at the time of manifestation of RA and between ACPA+ and ACPA- individuals. Conclusion: We show lower numbers of NK cells and classical monocytes and expansion of intermediate and non-classical monocytes in individuals in the preclinical phase of RA, especially in ACPA+ individuals. Such disproportion or pro-inflammatory potential of these cells was previously shown in the pathogenesis of established RA. We hypothesize that the dysregulation observed in at-risk individuals may be a prognostic marker and a predisposition leading to further development of RA. Acknowledgement: Projects AZV-17-32612A and MHCR 023728 Disclosure of Interests: Klára Prajzlerová: None declared, Olga Kryštfková: None declared, Petra Hánová: None declared, Hana Hulejova: None declared, Monika Gregová: None declared, Karel Pavelka: None declared, Jiří Vencovský Consultant for: Samsung, Speakers bureau: AbbVie, Novartis, Pfizer, Sanofi, Eli Lilly, Biogen, UCB, MSD, Werfen, Roche, Ladislav Šenolt Grant/research support from: AbbVie, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene Corporation, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Amgen, Takeda, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Mária Filková: None declared