Increased frequency of TIGIT+ CD4 T Cell subset in autoantibody-positive first-degree relatives of patients with rheumatoid arthritis

Abstract

BackgroundDespite immune cell dysregulation being an important event preceding the onset of rheumatoid arthritis (RA), the phenotype of T and B cells in preclinical RA is less understood. The aim of this study was to characterize T and B cell populations in RA patients and their autoantibody (aAb) negative and positive first-degree relatives (FDR).MethodsCryopreserved peripheral blood mononuclear cells (PBMCs) collected at scheduled visits from aAb-(n=25), and aAb+ FDR (n=10) and RA patients (n=13) were thawed and stained using optimized antibody cocktails as per a specific 13-color T or B cell panel. Immunophenotyping was performed using a Cytoflex LX (Beckman-Coulter) flow cytometer and FlowJo software was used for analyzing the frequency of immune cell populations.ResultsMulticolor flow cytometry experiments identified an increased TIGIT expression in circulating lymphocytes of aAb+ FDR and RA patients, relative to aAb- FDR (P<0.01). These TIGIT+ T cells exhibited a memory phenotype and expressed high levels of PD-1, ICOS, HLA-DR, CXCR3 and CXCR5. Moreover, increased TIGIT+ CD4 T cell frequency correlated with the frequency of PD-1+ CD4 T cells (r = 0.4705: P = 0.0043) and circulating levels of ACPA and RF. We also identified a decreased frequency of CD27+IgD- switched memory B cells in RA patients (P < 0.01), while increased frequency of TIGIT+ CD4 T cells in FDR correlated with the frequency of PD1+PTEN+ B cells (r = 0.6838, P = 0.0004) and autoantibody positivity (P = 0.01).ConclusionWe demonstrate TIGIT as a distinct CD4 T cell marker for differentiating aAb- FDR from aAb+FDR and might play a critical role in regulating T and B cell crosstalk in preclinical RA.

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

“…The co-expression of TIGIT and PD-1 on CD4+T cells has been linked to autoantibody production and RA activity [ 45 ]. First-degree relatives who are autoantibody-positive have a higher prevalence of TIGIT+ CD4 T cells [ 46 ]. Consequently, TIGIT expression on CD4 T cells is crucial for the production of autoantibodies by B cells in RA.…”

Pathogenesis of rheumatoid arthritis: one year in review 2023

“…• CD4 T-cell polyfunctionality might be active since early phases of RA in the synovial tissue. Increased frequencies of TIGIT-T cells in the blood, Tfh and B cells in the synovial tissue as well as CD4+ and CD8+ Tfh cells in the lymphoid tissue have been detected (56). • Newly identified age-associated B cells (ABCs) activate FLS through TNF-α-mediated pathways and have distinct transcriptomic properties affecting their ability to migrate into inflammatory joints (61).…”