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Characterization of senescence biomarkers in rheumatoid arthritis: relevance to disease progression

  • Laura E. Petersen
  • Jaqueline B. Schuch
  • Lucas A. de Azeredo
  • Talita S. A. Baptista
  • Julia G. Motta
  • Aline D. do Prado
  • Moisés Evandro BauerEmail author
Brief Report
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Abstract

Rheumatoid arthritis (RA) has been associated with early senescent features. However, the effects of disease progression on senescence markers are largely unknown. Here, we evaluated key senescence markers in RA, including telomere length and T cell differentiation stages as well as cytomegalovirus (CMV) serology, previously associated with premature aging. In a cross-sectional study, 44 patients with active (Ac-RA), 26 patients with controlled (Co-RA), and 30 healthy controls were recruited. Peripheral blood was collected and differentiation stages of T cells analyzed by multi-color flow cytometry. Enzyme-linked immunosorbent assays were used to evaluate the CMV serology. The telomere length was measured by multiplex quantitative PCR. Patients with Ac-RA presented lower percentage of intermediate-differentiated T cells (CD4+CD27-CD28+ and CD8+CD27-CD28+; p < 0.001). All patients had a reduced proportion of cytotoxic T cells, and higher CD4/CD8 ratio compared with controls (p < 0.001). A lower proportion of CMV IgG+ subjects was found in the Co-RA group, (P < 0.001), although no differences in the CMV IgG titers were observed between groups. The groups had similar leukocyte telomere length. In addition, age was negatively correlated with CD8+CD27+CD28+ T (early-differentiated) cells (P < 0.05). Positive correlations between CMV IgG titers and age (P < 0.05) and CD4+CD27-CD28- T (late-differentiated) cells (P < 0.01) were observed. Furthermore, disease duration was correlated with CD4+CD27+CD28+ T cells (r = − 0.318, p < 0.05) and CD4+CD27-CD28- T cells (r = 0.308, p < 0.05). Our findings indicate that CMV and age may have a similar impact on T cells in both RA patients and controls.

Key Points

• Patients and controls were homogenous regarding CMV IgG titers and TL.

• A lower proportion of CMV IgG+ subjects was found in the Co-RA group.

• Anti-CMV levels were positively correlated with age and percentage of CD4+CD27-CD28- (late-differentiated) T cells.

Keywords

Cytomegalovirus Differentiation of T cells Disease activity RA Telomere length 

Notes

Acknowledgments

We are very grateful to the patients and staff of São Lucas Hospital (Porto Alegre, Brazil).

Funding information

This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES - Finance Code 001).

Compliance with ethical standards

The institutional review board approved this study and all patients provided written informed consent for participation.

Disclosures

None.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Laboratory of Stress Immunology, School of SciencesPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  2. 2.Graduate Program in Biomedical GerontologyPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  3. 3.Graduate Program in Medical and Health SciencesPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  4. 4.Developmental Cognitive Neuroscience Laboratory (GNCD)Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  5. 5.Rheumatology ServiceNossa Senhora da Conceição Hospital – Grupo Hospitalar Conceição (GHC)Porto AlegreBrazil

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