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Abstract Number: 1747

A Newly Described Cytokine interleukin-40 Is Increased in the Serum of Individuals At-risk of Rheumatoid Arthritis and Induces an Inflammatory Response in Mononuclear Cells

Adela Navratilova1, Klára Prajzlerová2, Nora Růžičková3, Karel Pavelka4, Jiri Vencovsky5, Ladislav Senolt6, Maria Filkova3 and Lucie Andrés Cerezo3, 1Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Hlavní město Praha, Czech Republic, 2Institute of Rheumatology, Prague, Czech Republic, 3Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 4Institut of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Praha, Czech Republic, 5Institute of Rheumatology, Prague, Czech Republic, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, 6Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Praha, Czech Republic

Meeting: ACR Convergence 2023

Keywords: Biomarkers, Interleukins, rheumatoid arthritis

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Session Information

Date: Tuesday, November 14, 2023

Title: (1734–1775) RA – Etiology and Pathogenesis Poster

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Interleukin-40 (IL-40) is a newly described cytokine related to malignancies and immunity function. We have previously shown that IL-40 is up-regulated in early stages of rheumatoid arthritis (RA) and associates with processes that are thought to fuel the immune response. As the period preceding clinically apparent RA has not yet been fully described with respect to clinical biomarkers, we aimed to investigate IL-40 in individuals at-risk of RA development and its involvement in immune regulation in peripheral blood mononuclear cells (PBMCs).

Methods: IL-40 was analysed in the serum of individuals at-risk of RA (n=179, defined as patients with arthralgia with no clinical arthritis who are either carriers of anti-citrullinated protein antibodies, ACPA, or meeting the EULAR definition of clinically suspect arthralgia at baseline) and at the time of arthritis manifestation in patients who progressed to clinical arthritis (n=25). IL-40 was determined in the serum of age and sex-matched healthy controls (n=60). In vitro experiments were performed on PBMCs from at-risk individuals (n=10). Levels of IL-40 and IL-6 were measured by commercially available ELISA kits.

Results: IL-40 is up-regulated in at-risk individuals compared to healthy controls(p< 0.0001) and the levels of IL-40 are higher in the serum of double-positive (ACPA/rheumatoid factor) compared to double-negative at-risk individuals (p< 0.05). Out of 175 at-risk individuals, 25 developed clinical arthritis (with median 8.17 months of follow up); however, we have not found a significant difference in the levels of IL-40 at baseline, and at the time of arthritis manifestation. In vitro, PBMCs from at-risk individuals exposed to recombinant IL-40 strongly enhance the secretion of IL-6 in a dose-dependent manner when compared to unstimulated cells (IL-40: 10 ng/ml, p< 0.05; 50, 100, 250 ng/ml, p< 0.01). Furthermore, the application of NFkB inhibitor to the PBMCs prior to the exposure to IL-40 significantly reduced the secretion of IL-6 when compared to IL-40 treated cells without inhibition (p=0.004).

Conclusion: Here we show for the first time that IL-40 is elevated in the serum of individuals at-risk of RA. Moreover, results imply that systemically elevated IL-40 induces the pro-inflammatory response in PBMCs at-risk individuals via NFkB dependent pathway.


Disclosures: A. Navratilova: None; K. Prajzlerová: None; N. Růžičková: None; K. Pavelka: Abbvie, 2, 6, Amgen, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, Egis, 2, 6, MSD, 2, 6, Pfizer, 2, 6, Roche, 2, 6, UCB, 2, 6; J. Vencovsky: Argenx, 2, Eli Lilly, 6, Galapagos, 2, Horizon, 2, Merck, 2; L. Senolt: None; M. Filkova: None; L. Andrés Cerezo: None.

To cite this abstract in AMA style:

Navratilova A, Prajzlerová K, Růžičková N, Pavelka K, Vencovsky J, Senolt L, Filkova M, Andrés Cerezo L. A Newly Described Cytokine interleukin-40 Is Increased in the Serum of Individuals At-risk of Rheumatoid Arthritis and Induces an Inflammatory Response in Mononuclear Cells [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/a-newly-described-cytokine-interleukin-40-is-increased-in-the-serum-of-individuals-at-risk-of-rheumatoid-arthritis-and-induces-an-inflammatory-response-in-mononuclear-cells/. Accessed .
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