Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Co-inhibitory receptors (Co-IRs) are critical for regulating T cell activation and preventing immunopathology in rheumatoid arthritis (RA).
• Understanding the expression of Co-IRs on T cells and soluble Co-IR levels in RA patients is essential for disease management.

Purpose of the Study:

• To determine the phenotypic expression of Co-IR T cells in Taiwanese RA patients.
• To measure serum levels of soluble PD-1, PDL-2, and TIM3 in RA patients.
• To assess the correlation between Co-IR T cell expression, soluble Co-IR levels, and clinical indicators of RA disease activity.

Main Methods:

• Multicolor flow cytometry was used to immunophenotype T cells expressing Co-IRs.
• Enzyme-linked immunosorbent assay (ELISA) quantified serum levels of soluble PD-1, PDL-2, and TIM3.
• Correlations were analyzed between Co-IR expression (MFI and percentage) and clinical markers such as ESR, hsCRP, and DAS28 scores.

Main Results:

• Elevated levels of PD-1 (CD279), CTLA-4, and TIGIT were observed on CD4+ T cells, and TIGIT, HLA-DR, TIM3, and LAG3 on CD8+ T cells in RA patients.
• Specific Co-IR expressions on CD4+ and CD8+ T cells correlated significantly with hsCRP, ESR, and DAS28 scores.
• Serum levels of soluble PD-1, PDL-2, and TIM3 were markedly elevated in RA patients and correlated with specific T cell Co-IR expressions.

Conclusions:

• Co-IR expression on CD4+ and CD8+ T cells, along with elevated serum soluble PD-1, PDL-2, and TIM3, are significantly associated with RA disease activity.
• These findings suggest that Co-IRs and their soluble forms may serve as potential biomarkers for disease activity and play a crucial role in RA pathogenesis.