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

Autor:	Anaparti V; Manitoba Center of Proteomics and Systems Biology, Departments of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada., Tanner S; Manitoba Center of Proteomics and Systems Biology, Departments of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada., Zhang C; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada., O'Neil L; Manitoba Center of Proteomics and Systems Biology, Departments of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.; Rheumatic Diseases Unit, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada., Smolik I; Rheumatic Diseases Unit, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada., Meng X; Manitoba Center of Proteomics and Systems Biology, Departments of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.; Rheumatic Diseases Unit, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada., Marshall AJ; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada., El-Gabalawy H; Manitoba Center of Proteomics and Systems Biology, Departments of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.; Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.; Rheumatic Diseases Unit, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jul 28; Vol. 13, pp. 932627. Date of Electronic Publication: 2022 Jul 28 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.932627
Abstrakt:	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: 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). 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Anaparti, Tanner, Zhang, O’Neil, Smolik, Meng, Marshall and El-Gabalawy.)
Databáze:	MEDLINE
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