Skip to main content
Top
Published in: Clinical Rheumatology 10/2019

01-10-2019 | Rheumatoid Arthritis | Brief Report

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

Authors: Laura E. Petersen, Jaqueline B. Schuch, Lucas A. de Azeredo, Talita S. A. Baptista, Julia G. Motta, Aline D. do Prado, Moisés Evandro Bauer

Published in: Clinical Rheumatology | Issue 10/2019

Login to get access

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.
Literature
3.
go back to reference Chalan P, van den Berg A, Kroesen B-J, Brouwer L, Boots A (2015) Rheumatoid arthritis, Immunosenescence and the hallmarks of aging. Curr Aging Sci 8:131–146CrossRef Chalan P, van den Berg A, Kroesen B-J, Brouwer L, Boots A (2015) Rheumatoid arthritis, Immunosenescence and the hallmarks of aging. Curr Aging Sci 8:131–146CrossRef
6.
go back to reference Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, Birch KE, Cook JE, Jackson SE, Salmon M, Rustin MH, Akbar AN (2005) Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol 175:8218–8225CrossRef Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, Birch KE, Cook JE, Jackson SE, Salmon M, Rustin MH, Akbar AN (2005) Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol 175:8218–8225CrossRef
7.
go back to reference Wikby A, Johansson B, Olsson J, Löfgren S, Nilsson BO, Ferguson F (2002) Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 37:445–453CrossRef Wikby A, Johansson B, Olsson J, Löfgren S, Nilsson BO, Ferguson F (2002) Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 37:445–453CrossRef
13.
go back to reference Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ (1999) Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence. J Immunol 162:6572–6579PubMed Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ (1999) Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence. J Immunol 162:6572–6579PubMed
14.
go back to reference Weyand CM, Fulbright JW, Goronzy JJ (2003) Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 38:833–841CrossRef Weyand CM, Fulbright JW, Goronzy JJ (2003) Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 38:833–841CrossRef
19.
22.
go back to reference Kipling D (2001) Telomeres, replicative senescence and human ageing. Maturitas 38:25–37 discussion 37-8CrossRef Kipling D (2001) Telomeres, replicative senescence and human ageing. Maturitas 38:25–37 discussion 37-8CrossRef
23.
go back to reference Antoniou KM, Margaritopoulos GA, Proklou A, Karagiannis K, Lasithiotaki I, Soufla G, Kastrinaki M, Spandidos DA, Papadaki HA, Siafakas NM (2012) Investigation of telomerase/telomeres system in bone marrow mesenchymal stem cells derived from IPF and RA-UIP. J Inflamm (Lond) 9:27. https://doi.org/10.1186/1476-9255-9-27 CrossRef Antoniou KM, Margaritopoulos GA, Proklou A, Karagiannis K, Lasithiotaki I, Soufla G, Kastrinaki M, Spandidos DA, Papadaki HA, Siafakas NM (2012) Investigation of telomerase/telomeres system in bone marrow mesenchymal stem cells derived from IPF and RA-UIP. J Inflamm (Lond) 9:27. https://​doi.​org/​10.​1186/​1476-9255-9-27 CrossRef
Metadata
Title
Characterization of senescence biomarkers in rheumatoid arthritis: relevance to disease progression
Authors
Laura E. Petersen
Jaqueline B. Schuch
Lucas A. de Azeredo
Talita S. A. Baptista
Julia G. Motta
Aline D. do Prado
Moisés Evandro Bauer
Publication date
01-10-2019
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 10/2019
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04615-0

Other articles of this Issue 10/2019

Clinical Rheumatology 10/2019 Go to the issue

Clinical Image

Popeye’s sign