Expanded T-Cell Clones Are Present in the Synovium before the Clinical Onset of Rheumatoid Arthritis

Giulia Balzaretti^1,2,3, Paul L. Klarenbeek⁴, Marieke E. Doorenspleet⁵, Maria JH de Hair⁶, Barbera C.D. van Schaik⁷, Rebecca Esveldt², Marleen van de Sande¹, Danielle Gerlag⁸, Antoine H.C. van Kampen⁷, Frank Baas^2,9, Paul-Peter Tak¹⁰ and Niek de Vries^3,5, ¹Clinical Immunology & Rheumatology, ARC | Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, ²Dept. of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, ³Dept. of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, ⁴Amsterdam Rheumatology & immunology Center | Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, ⁵Amsterdam Rheumatology and immunology Center | Academic Medical Center / University of Amsterdam, Amsterdam, Netherlands, ⁶Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands, Utrecht, Netherlands, ⁷Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, ⁸GlaxoSmithKline, Stevenage, United Kingdom, ⁹Dept. of Genome Diagnostics, Leiden University, Leiden, Netherlands, ¹⁰GlaxoSmithKline, Cambridge, United Kingdom

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: rheumatoid arthritis (RA) and rheumatoid arthritis, synovium, T cells

Session Information

Date: Tuesday, October 23, 2018

Title: 5T092 ACR Abstract: T Cell Biology & Targets in Autoimmune & Inflammatory Disease (2797–2801)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

In healthy individuals with arthralgia and RA-specific autoantibodies (so called at-risk individuals) the presence of expanded B-cell receptor (BCR) clones in peripheral blood (PB) accurately predicts who will develop arthritis in the short term¹. Following up on these observations, we investigated in the same cohort of at-risk individuals whether the T-cell receptor beta (TCRβ) repertoire characteristics in PB and synovial tissue (ST) might also predict imminent onset of arthritis.

Methods:

Next-Generation Sequencing of the TCRβ repertoire was performed on 20 randomly selected individuals with elevated IgM-RF and/or ACPA levels. Ten individuals did not develop RA during at least 3 years of follow-up, and 10 individuals did. Peripheral blood and synovial tissue samples were analysed during the at-risk phase and, for individuals that developed RA, again after RA onset. T-cell clones were identified by their unique TCRβ sequence².

Results:

In the at-risk phase, the synovium is already characterized by expanded TCRβ clones, both in at-risk individuals that will and will not develop arthritis later. These clones persist in the tissue during onset of arthritis. A higher impact of the dominant TCRβ clones in the synovial tissue in the at-risk phase was associated with longer time to arthritis (p=0.02).

Conclusion:

Expanded T-cell clones are present in the synovium of at-risk individuals regardless of future development of RA. The expanded clones are maintained after onset of clinical disease. Combined with literature data, these observations show that T cell clones are already expanded in ST very early in disease, and suggest an overall regulatory role. Further studies are needed to characterize these clones.

References:

¹Tak PP et al. Ann Rheum Dis. 2017.

²Klarenbeek PL et al. Immunol Lett. 2010.

Disclosure: G. Balzaretti, None; P. L. Klarenbeek, None; M. E. Doorenspleet, None; M. J. de Hair, None; B. C. D. van Schaik, None; R. Esveldt, None; M. van de Sande, None; D. Gerlag, None; A. H. C. van Kampen, None; F. Baas, None; P. P. Tak, None; N. de Vries, None.

To cite this abstract in AMA style:

Balzaretti G, Klarenbeek PL, Doorenspleet ME, de Hair MJ, van Schaik BCD, Esveldt R, van de Sande M, Gerlag D, van Kampen AHC, Baas F, Tak PP, de Vries N. Expanded T-Cell Clones Are Present in the Synovium before the Clinical Onset of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/expanded-t-cell-clones-are-present-in-the-synovium-before-the-clinical-onset-of-rheumatoid-arthritis/. Accessed .

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