Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

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.

Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson / Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases

Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. [...] (AU)

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. (AU)

The presence of IFL3/4 rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus.

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.

Biological role of excretory-secretory proteins in endemic parasites of Latin America and the Caribbean.

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.

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. / Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson.

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.

Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis.

Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4(+) CD45RO(+) forkhead box protein 3 (FoxP3)(high) and CD4(+) CD25(high) FoxP3(+) CD95(high) phenotype and of non-regulatory CD4(+) CD45RO(+) FoxP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4(+) CD38(+) ). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.

Immunopathology in Taenia solium neurocysticercosis.

Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented.

Leukocytes and the kidney contribute to interstitial inflammation in lupus nephritis.

Interstitial leucocyte infiltration, a prominent feature of lupus nephritis, predicts deterioration of renal function. We used two models of lupus nephritis in mice, one with chronic spontaneous disease and the other with acute interferon-alpha (IFN alpha)-mediated disease. The latter is characterized by the virtual absence of interstitial infiltration. In vivo migration assays showed that splenic leukocytes from spontaneously nephritic mice tended to migrate into non-inflamed syngeneic kidneys. This was enhanced if the recipient kidneys were already inflamed. Kidneys from both chronically and acutely nephritic mice showed similar ability to recruit splenic leukocytes from chronically diseased mice. Leukocytes from acutely diseased mice, however, failed to migrate into chronically inflamed kidney. Compared with those with chronic nephritis, the kidneys of acute nephritic mice expressed less of the inflammatory chemokine CXCL13/BLC. Moreover, leukocytes from acute nephritic mice displayed impaired migration, in vitro, to T-cell chemokine attractants. This study links leukocyte infiltration to both kidney chemokine expression, and leukocyte chemotaxis to kidney-expressed chemokines.

Impact of highly active antiretroviral therapy on the maturation of anti-HIV-1 antibodies during primary HIV-1 infection.

OBJECTIVES: To study the impact of highly active antiretroviral therapy (HAART) on isotype switching and avidity maturation of HIV-1-specific immunoglobulin G (IgG) in patients with primary HIV-1 infection (PHI). METHODS: We studied the emergence and the evolution of anti-HIV IgG antibodies by quantitative immunoblotting to analyse IgG subclasses and IgG avidity. Serum samples were obtained from 16 PHI patients from the French PRIMO Cohort Study at various points in the first year of infection: eight patients received no treatment (group I), and eight patients received efficient HAART (group II) during the study period. RESULTS: Early initiation of HAART in PHI patients partially prevented an increase in anti-HIV-1 IgG levels. Within IgG subclasses, the amount of anti-HIV-1 IgG1 gradually increased with time in both groups, although levels remained lower in treated patients. The anti-p24 IgG2 level was always lower in group II. We observed a decrease in anti-p24 IgG3 over time in both groups. Treatment did not affect the maturation of HIV-1 IgG avidity, which increased in both groups until month 3 and then remained high until the end of the 12-month follow-up period. CONCLUSIONS: HAART in PHI partially prevents the emergence of HIV-1 IgG antibodies, but does not affect the quality of these antibodies, as reflected in their isotype and avidity.