Artrite reumatóide como modelo de imunossenescência prematura

Abstract

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, naïve/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, naïve 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.