A relação entre biomarcadores periféricos e funções cognitivas em pacientes com artrite reumatóide

• Autor(a) principal: Petersen, Laura Esteves
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
• Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/7984
• topic: Artrite Reumatoide; Cognição; Células B; Citocinas; Fatores Neurotróficos; Imunossenescência Prematura; Citomegalovírus; CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Rheumatoid Arthritis (RA) is an autoimmune and inflammatory disease which leads to premature immunosenescence and the development of articular and extra-articular manifestations, including joint damage and cognitive dysfunction, respectively. Peripheral immune system cells and the chronic inflammation, both of great importance for RA, are potentials mechanisms involved in cognitive dysfunction. In contrast, experimental studies have shown the beneficial contribution of immune cells, mainly T cells reactive to central nervous system (CNS) antigens, to neurogenesis and neuroplasticity. Previous data have shown that RA patients besides to have worse performance in cognitive tests, have significantly lower levels of B cells and higher levels of senescent T cells (CD8+CD28-). However, is not known yet which B cells subpopulations are related to poor cognitive performance, if clinical severity of disease (active and controlled disease) impacts on cognition and which factor is responsible for remodeling of peripheral immunity (immunosenescence). Hypotheses about the contribution of latent infections (Cytomegalovirus; CMV), for the development of immunosenescence (observed by telomere shortening and increase of CD28- cells) have been raised. However, it remains in discussion the CMV soroprevalence and its relation with the development of premature immunological senesce in RA. Based on this findings, in this work we have broadly assessment the cognition of RA patients with active and controlled disease, peripheral levels of lymphocytes subsets (T and B cells), neurotrophic factors, cytokines besides that CMV soroprevalence and immunosenescence profile (telomere length and CD28- cells). This work also proposed to explore the relationship between immune mediators, neurotrophic factors and cognitive performance, besides the association between CMV and immunosenescence. For this purpose, 102 RA patients (67 active and 35 controlled disease) and 30 healthy controls adjusted for age, gender and schooling were recruited. The cognitive function, levels of stress and depression were assessment by means of neurocognitive tests (Mini Mental State Examination, Logical memory, digit span, Trail Making Test, N-back, Stroop word-colors) and specific questionnaires (Beck Depression Inventory –II for depression and Perceived Stress Scale for stress). Twenty ml of blood were collected and, after plasma separation, the peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation gradient. PBMCs were immunophenotyped by flow cytometry to investigate the frequency of T and B cells subsets. The genomic DNA was isolated from PBMCs and the telomere length was evaluated by real time PCR. Neurotrophic factors, cytokines, IgM and IgG anti-CMV were measured in plasma by means of ELISA (NF and CMV) and Citometric Bead Array (CBA; cytokines). In general, patients with active disease had worse cognitive performance, followed by patients with controlled disease producing cells, in addition to high levels of cytokines, with the exception of IL-17A. Higher levels of BDNF were found in patients with active RA followed by controlled disease and control group. The peripheral levels of GDNF were lower in patients with active RA than control group. The IL-6 was predictor of the performance in Trail Making test. IgM and IgG anti-CMV antibody titers did not differ between patients and controls. Only IgG anti-CMV was positively associated with age and senescent cells. In conclusion, RA patients with active disease had worse performance in cognitive tasks that were related to peripheral immune mediators (cells and cytokines). Besides that, we found that late infection (IgG) by CMV were associated only with CD4+CD27-CD28- and haven’t correlated with other immunosenescence characteristics. However, understand in which sense e how the relationship between the peripheral environment and the CNS is established, may contribute to development of preventive interventions to cognitive impairments and premature immunosenescence, since both factors are associated to health and well-being of individuals.