Background: Despite 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).

Methods: Cryopreserved 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.

Results: Multicolor 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: = 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 ( < 0.01), while increased frequency of TIGIT+ CD4 T cells in FDR correlated with the frequency of PD1PTEN B cells (r = 0.6838, = 0.0004) and autoantibody positivity ( = 0.01).

Conclusion: We 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366176PMC
http://dx.doi.org/10.3389/fimmu.2022.932627DOI Listing

Publication Analysis

Top Keywords

first-degree relatives
8
rheumatoid arthritis
8
immune cell
8
aab+ fdr
8
cell
5
increased frequency
4
frequency tigit+
4
tigit+ cd4
4
cd4 cell
4
cell subset
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!