Limited Regulatory T Cell Response in Post-Chikungunya Viral Arthritis: A Therapeutic Opportunity?

Aileen Chang¹, Sarah Tritsch¹, Carlos Herrera¹, Liliana Encinales², Andres Cadena³, Wendy Rosales⁴, Evelyn Mendoza⁵, Samuel Simmens¹, Richard Amdur⁶, Paige Fierbaugh¹, Abigale Proctor¹, Alfonso Sucerquia¹, Christopher Mores¹, David Boyle⁷, Gary Firestein⁷ and Gary Simon¹, ¹George Washington University, Washington, DC, ²Allied Research Society, Barranquilla, Colombia, ³Clinica de la Costa, Barranquilla, Colombia, ⁴Universidad Libre, Barranquilla, Colombia, ⁵Universidad Libre, Bogotá, Colombia, ⁶Northwell, Washington, DC, ⁷University of California San Diego, San Diego, CA

Meeting: ACR Convergence 2023

Keywords: Arthritis, Infectious, T Cell

Session Information

Date: Sunday, November 12, 2023

Title: (0196–0228) Infection-related Rheumatic Disease Poster

Session Type: Poster Session A

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

Background/Purpose: The objective was to define the relationship between chronic chikungunya (CHIKV) post-viral arthritis disease severity, interleukin (IL)-2, and T cell subsets in order to determine if arthritis therapies targeting enhanced regulatory T cell (Treg) activity such as low-dose IL-2 may provide benefit.

Methods: Participants with CHIKV arthritis were recruited from Colombia from 2019–2021. Arthritis disease severity was quantified using the Disease Activity Score (DAS)-28 and an Arthritis-Flare Questionnaire adapted for CHIKV arthritis. Plasma cytokine concentrations (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood Treg subsets were measured using flow cytometry.

Results: Among participants with CHIKV arthritis (N=158),IL-2 levels and frequency of Tregs were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 without increases in IL-2 (p< 0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p< 0.05) without affecting Teff frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4⁺ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p< 0.05).

Conclusion: CHIKV arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers, suggesting that low-dose IL-2 therapies targeting enhanced Treg activity may be a plausible objective for further investigation.

Increasing IL_2 in chikungunya arthritis is associated with increased Treg numbers and expression of immunomodulatory markers. Herein we report that higher levels of IL_2 in chikungunya arthritis patients were associated with greater numbers of Tregs. Greater IL_2 was also associated with enhanced expression of CTLA_4, which suppresses effector T cell activation by decreasing antigen presenting cell costimulatory function (CD80/CD86). Additionally, higher IL_2 levels of IL_2 were associated with higher expression of HLA-DR, which functions in Treg activation; CD45RA, found in resting Tregs; and Helios, a transcription factor that acts on the Foxp3 promotor to increase immunosuppressor function. Last, increased IL_2 levels correlated with decreased CCR7, whose deficiency permits Treg retention in inflamed tissue.

Disclosures: A. Chang: None; S. Tritsch: None; C. Herrera: None; L. Encinales: None; A. Cadena: None; W. Rosales: None; E. Mendoza: None; S. Simmens: None; R. Amdur: None; P. Fierbaugh: None; A. Proctor: None; A. Sucerquia: None; C. Mores: None; D. Boyle: None; G. Firestein: Eli Lilly, 5; G. Simon: None.

To cite this abstract in AMA style:

Chang A, Tritsch S, Herrera C, Encinales L, Cadena A, Rosales W, Mendoza E, Simmens S, Amdur R, Fierbaugh P, Proctor A, Sucerquia A, Mores C, Boyle D, Firestein G, Simon G. Limited Regulatory T Cell Response in Post-Chikungunya Viral Arthritis: A Therapeutic Opportunity? [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/limited-regulatory-t-cell-response-in-post-chikungunya-viral-arthritis-a-therapeutic-opportunity/. Accessed .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/limited-regulatory-t-cell-response-in-post-chikungunya-viral-arthritis-a-therapeutic-opportunity/