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Previous issue date: 2013-03-27 / The rheumatoid arthritis (RA) is an autoimmune disease, besides the physical damage, the RA has been associated with premature aging of the immune system (immunosenescence) and age-related morbidities, including a decline in cognitive functioning. Factors such as chronic inflammation and the use of glucocorticoids (GCs) for a long time, both related to RA, are potential mechanisms involved in cognitive dysfunction in the general population. Experimental studies have shown the beneficial contribution of immune cells on the central nervous system (CNS). Moreover, disorders, such as mild cognitive impairment and Alzheimer s disease, exhibit alterations in peripheral lymphocytes subtypes. Based on this, here we explore the relationship between cognitive function, disease activity score (DAS-28) and lymphocytes subsets in RA. Thirty patients with RA and 19 healthy controls, which did not differ significantly in sex, age and schooling were recruited in this study. Cognitive function (MMSE, logic and working memory), stress and depression were assessment through interviews where specific clinical questionnaires were applied. Lymphocytes were isolated from mononuclear cells of peripheral blood (PBMCs) and immuphenotyped by flow cytometry to investigate the following lymphocytes subsets: B cells, activated T cells, na?ve/memory T cells, regulatory FoxP3+ T cells, IL-17+ cells, natural killer (NK) cells, and senescence-associated CD28- T cells. RA patients had a lower cognitive performance on the MMSE, logical and working memory compared to healthy controls. Though, all individuals in both groups had a score higher than the cutoff point established by the MMSE. The time use of GC and the C-reactive protein (CRP) levels did not correlated with cognitive assessment. Patients had an increased proportions of regulatory T cells, na?ve CD4+ T cells and senesce-associated T cells (CD28-), but lowered percentages of B and memory CD8+ T cells compared to healthy controls. Early activated T cells (CD3+CD69+) and CD8+CD28- T cells were found negatively associated with cognition. Concluding, patients with RA have a lower cognitive performance compared to healthy controls. GC and CRP were not correlated with memory; however expansions of activated and senescence-associated T cells were correlated with poor memory performance. / A artrite reumatoide (AR) ? uma doen?a autoimune, que al?m da presen?a de danos f?sicos, tem sido associada com o envelhecimento prematuro do sistema imune (imunossenesc?ncia) e morbidades relacionadas ? idade, incluindo decl?nio no funcionamento cognitivo. Fatores como a inflama??o cr?nica e o uso de glicocorticoides (GCs), ambos relacionados a AR, s?o potenciais mecanismos envolvidos com a disfun??o cognitiva na popula??o geral. Estudos experimentais tem revelado a contribui??o ben?fica das c?lulas imunol?gicas sobre o sistema nervoso central (SNC). Al?m disto, patologias como o dano cognitivo leve e doen?a de Alzheimer apresentam altera??es nos subtipos linfocit?rios perif?ricos. Com base nisto, neste trabalho nos exploramos as rela??es entre fun??o cognitiva, score de atividade da doen?a (DAS-28), e subtipos linfocit?rios na AR. Trinta pacientes com AR e dezenove controles saud?veis, que n?o diferiram significativamente em rela??o a sexo, idade e escolaridade, foram recrutados neste estudo. A fun??o cognitiva (mini-exame do estado mental - MMSE, mem?ria l?gica e mem?ria de trabalho), estresse e depress?o foram avaliados atrav?s de entrevistas onde foram aplicados question?rios cl?nicos espec?ficos. Os linf?citos foram isolados das c?lulas mononucleares do sangue perif?rico (PBMCs), e imunofenotipados por citometria de fluxo para investigar a presen?a dos seguintes subgrupos: c?lulas B, c?lulas T ativadas, c?lulas T naive/mem?ria, c?lulas T regulat?ria (reg) CD4+FoxP3+, c?lulas IL-17+, c?lulas natural killer (NK), e c?lulas T CD28- associadas a senesc?ncia. Os pacientes com AR tiveram um desempenho cognitivo inferior no MMSE, mem?ria l?gica e mem?ria de trabalho se comparado a controles saud?veis. Embora todos os indiv?duos, de ambos os grupos, tiveram uma pontua??o superior ? estabelecida pelo cutoff do MMSE. O tempo de uso de GCs e os n?veis de prote?na C - reativa (PCR) n?o se correlacionaram com avalia??o cognitiva. Os pacientes tem aumento nas propor??es de c?lulas Treg, c?lulas T CD4+ naive e c?lulas T associadas a senesc?ncia (CD28), mas baixas porcentagens de c?lulas B e c?lulas T CD8+ de mem?ria do que controles saud?veis. C?lulas T rec?m ativadas e c?lulas T CD8+CD28- foram negativamente associadas com a cogni??o. Concluindo, pacientes com AR tem um desempenho cognitivo inferior se comparado a controles saud?veis. GCs e PCR n?o se correlacionaram com mem?ria, no entanto, expans?o da popula??o de c?lulas T ativadas e c?lulas T associadas ? senesc?ncia foram correlacionadas com performance de mem?ria.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/5466 |
| Date | 27 March 2013 |
| Creators | Petersen, Laura Esteves |
| Contributors | Bauer, Mois?s Evandro |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biologia Celular e Molecular, PUCRS, BR, Faculdade de Bioci?ncias |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 8198246930096637360, 600, 600, 36528317262667714 |
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