RESUMO
INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.
Assuntos
Doença de Alzheimer , Doença de Parkinson , Linfócitos T CD4-Positivos , Citometria de Fluxo , Humanos , FenótipoRESUMO
OBJECTIVE: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. RESULTS: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. CONCLUSIONS: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.
Assuntos
Quimiocina CXCL10/sangue , Interferons/genética , Interleucinas/genética , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.