Extracellular Vesicles in the Circulating of Rheumatoid Arthritis Patients Are Pro-Inflammatory

Onno J. Arntz¹, Bartijn C.H. Pieters¹, Rogier Thurlings², Peter L. E. M. van Lent³, Peter M. van der Kraan³, Marije I. Koenders¹, FHJ van den Hoogen² and Fons A.J. van de Loo¹, ¹Experimental Rheumatology, Radboudumc, Nijmegen, Netherlands, ²Rheumatology, Radboudumc, Nijmegen, Netherlands, ³Experimental Rheumatology, Radboud university medical center, Nijmegen, Netherlands

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Rheumatoid arthritis (RA)

Session Information

Date: Monday, November 14, 2016

Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis - Poster I

Session Type: ACR Poster Session B

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

Background/Purpose: Rheumatoid arthritis (RA) is a progressive and degenerative joint disease with chronic synovial inflammation in multiple joints. Interestingly, the symmetry and spreading of the disease to multiple joints are clinically significant signs of RA, but not fully understood. Our hypothesis is that circulating extracellular vesicles (cEVs) obtained from blood of RA patients contribute to the polyarticular and systemic involvement of this disease. In this study we measured cytokines in platelet free plasma (PFP) and plasma EVs from RA patients and healthy controls (HC). Furthermore, we analyzed the biological activity of cEVs using functional studies in human monocytes (THP-1).

Methods: cEVs were obtained sterile from PFP of 21 RA patients or 15 HC (age matched) by size exclusion chromatography (SEC). Protein content of cEVs was measured by micro-BCA and characterized by Nanoparticle Tracking Analysis and electron microscopy. Level of TNFα, IL-1β, IL-6, IL-8, IL-10 and MCP-1 in PFP and cEVs were measured by Luminex. To study the functionality, 50.000 THP-1 cells were incubated for 24h with RA- or HC-cEVs and cytokine production was measured in supernatant by Luminex.

Results: The particle size and concentration of RA-cEVs (105 nm, 4.74 x10¹⁰particles/ml) were not different from HC-cEVs (106 nm, 4.40×10¹⁰ particles/ml). Protein content was also not significant different (RA;211 µg/ml, HC;176 µg/ml). In RA-cEVs the levels of TNFα, IL-1β, IL-6, IL-10 and MCP-1 were significant enhanced (RA-cEVs: 71,8,30,22 and 26 pg/ml ; HC-cEVs: 1,0,3,0 and 9 pg/ml resp.) while in PFP only levels of IL-1β and IL-6 were significant increased (RA-cEVs: 15 and 112 pg/ml, HC-cEVs: 1 and 5 pg/ml resp.). THP-1 cells exposed to cEVs were activated shown by enhanced production of IL-8. Cells incubated with RA-cEVs showed significant higher protein production of MCP-1 (45%) while TNFα, IL-1β and IL-6 were undetectable.

Conclusion: This study showed that cEVs obtained from platelet free plasma of RA patients contains cytokines and were able to stimulate THP-1 cells to release pro-inflammatory proteins. For that, it is plausible that cEVs contribute to the systemic nature of this disease.

Disclosure: O. J. Arntz, None; B. C. H. Pieters, None; R. Thurlings, None; P. L. E. M. van Lent, None; P. M. van der Kraan, None; M. I. Koenders, None; F. van den Hoogen, None; F. A. J. van de Loo, None.

To cite this abstract in AMA style:

Arntz OJ, Pieters BCH, Thurlings R, van Lent PLEM, van der Kraan PM, Koenders MI, van den Hoogen F, van de Loo FAJ. Extracellular Vesicles in the Circulating of Rheumatoid Arthritis Patients Are Pro-Inflammatory [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/extracellular-vesicles-in-the-circulating-of-rheumatoid-arthritis-patients-are-pro-inflammatory/. Accessed .

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