IL-6 secretion of CD4+ T cells stimulated by LC3-positive extracellular vesicles in human epithelial ovarian cancer

Ovarian cancer (OC) as the most fatal gynecological malignancy worldwide, with epithelial ovarian cancer (EOC) being the predominant and most lethal form, poses a serious threat to human health. LC3-positive extracellular vesicles (LC3+ EVs) promote tumorigenesis by educating CD4+ T cells in a murine melanoma model. However, regulation of LC3+ EVs in human EOC remains largely unknown. MethodsDifferential analysis of Rab8a, Hsp90α and Il6 expression was performed using GEPIA2. The number of LC3+ EVs and the frequency of Heat shock protein 90α+ LC3+ EVs (HSP90α+ LC3+ EVs) in the ascites of EOC patients were tested by flow cytometry. IL-6, IL-10, IFN-γ, IL-4 and TGF-β were measured by ELISA. CD4+ T cells were isolated from peripheral blood of healthy human donors using MACS magnetic bead technology. ResultsHigher Rab8a, Hsp90a and Il6 expression of cancer tissues compared with normal adjacent tissues in OC were found. The level of IL-6 was positively correlated with LC3+ EVs number, HSP90α+ LC3+ EVs percentage in the ascites, and ROMA index of the patient. In addition, elevated IL-6 production by CD4+ T cells induced by LC3+ EVs was observed, which was suppressed by anti-HSP90α or anti-TLR2. ConclusionsLC3+ EVs level and HSP90α+ LC3+ EVs percentage were associated with elevated IL-6 in the ascites of EOC patients. HSP90α on LC3+ EVs from human EOC could stimulate CD4+ T cell production of IL-6 via TLR2. (AU)

Identificación de la función de las células T en los microambientes del cáncer de pulmón

PurposeTo investigate whether γδ1 T cells derived from lung cancer tissues have immunosuppressive function and to verify the mechanism of immunosuppressive effect.MethodsFresh lung cancer tissue samples were collected, some of them were prepared tissue sections, the others were isolated and amplified into TILs cells, γδ1 T cells were isolated from TILs cells by immunomagnetic beads kits, and then cloned and amplified. The immunomodulatory effects of γδ1 T cells on naive and effector CD4+ T cells were detected by immunohistochemistry, flow cytometry, CCK8, ELISA and transwell culture.ResultsA high proportion of γδ1 T cells was found in lung cancer tissues. The cultural supernatants of γδ1 T cells could inhibit the proliferation of naive CD4+ T cells and decrease the secretion level of IL-2 by effector CD4+ T cells. Further studies showed that the expression levels of IL-8, MIP-1α, MIP-1β and RANTES were higher than that of IFN-γ, GM-CSF and TNF-α, TNF-β, however, their neutralizing antibodies could not block the immunosuppressive activity of the supernatant.Conclusionγδ1 T cells play an negative immunoregulation function in lung cancer microenvironments, and have obvious immunosuppressive effects on proliferation and cytokine release of naive CD4+ T cells and effector CD4+ T cells. Preliminary evidence from this study suggests that the mechanism of immunosuppressive effects is mediated by the soluble factors in γδ1 T cell culture supernatants, but its exact molecular mechanism needs to be further explored.

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)

Oral Kaposi sarcoma development is associated with HIV viral load, CD4+ count and CD4+/CD8+ ratio / El desarrollo del sarcoma de Kaposi oral está asociado con carga viral de VIH, recuento de CD4+ y relación CD4+/CD8+

Background: Kaposi’s sarcoma (KS) is an uncommon, multifocal and angioproliferative lesion, which demon-strates a poor prognosis. The aim of the present research was to explore the association of HIV viral load, CD4+and CD8+ counts and the CD4+/CD8+ ratio on the risk of oral Kaposi’s sarcoma (KS) development.Material and Methods: A total of 62 patients were retrieved from March 2008 to October 2020 from the files oftwo oral pathology centres. Clinical, laboratory and follow-up data were retrieved from their medical files. Poissonregression was used to explore the role of history of immunosuppression and its association with oral KS develop-ment. A P-value <0.05 was considered significant.Results: Sixty-two patients were included in the present study (32 with oral KS and 30 with no presentation oflesions anywhere on the body). Patients with oral KS presented a mean age of 32.6 years, and male patients weremore affected. The hard palate (15 cases; 46.8%) was the main anatomical site affected. The lesions were mostlypresented as swellings (13 cases; 40.6%) and nodules (12 cases; 37.5%). Systemic manifestations were also ob-served, including candidiasis (4 cases; 12.5%), bacterial infection (3 cases; 9.3%), tuberculosis (3 cases; 9.3%),herpes simplex (3 cases; 9.3%) and pneumonia (3 cases; 9.3%). A significant correlation was observed betweenHIV viral load, CD4+ count and the CD4+/CD8+ ratio with oral KS development.Conclusions: HIV viral load, CD4+ count and the CD4+/CD8+ ratio are associated with oral KS development.(AU)

Effect of strength training on people with HIV and immunometabolic disorders / Efecto del entrenamiento de fuerza en personas con VIH y trastornos inmunometabólicos

The introduction of highly active antiretroviral therapy (HAART) was able to help to control viral condition in patients livingwith HIV/AIDS, diminishing virus concentration and increasing T CD4 + cells. However, adverse effects follow the treatment,like lipodystrophy syndrome, characterized by morphological changes in body fat distribution and changes serum lipids andglycides levels, increasing the risk for chronical diseases with cardiovascular effects. Thus, complimentary non-drug practices,as strength training, are essential to treat these patients, helping to improve their immunometabolic condition, leading to abetter coping with the disease. The aim of this study was to investigate the influence of a 12-week strength training protocolon immunometabolic system of people living with HIV/AIDS. It is a quasi-experimental study, conducted on 20 patients (16men), all living with HIV/AIDS using HAART. T CD4 + cell numbers, serum triglycerides, cholesterol (total and fractions) andglycemia were measured before and after training. The data underwent to descriptive statistics using a paired T test, withthe significance level set at p <0.05.There was a significant increase of 15.4% (p=0.009) on T CD4 + cells and, although notstatistically significant, reduction on glycemia, total cholesterol and triglycerides and increase on HDL-cholesterol fraction.So, it is suggested that strength training may be effective on immunometabolic condition of people living with HIV / AIDS,increasing T CD4+ cells and controlling serum levels of lipids and glycides.(AU)

La introducción de la terapia antirretroviral altamente activa (HAART) ayudó a controlar la condición viral de los pacientes con HIV/AIDS, reduciendo la concentración del virus y aumentando las células T CD4 +. Sin embargo, los efectos adversos acompañan el tratamiento, como el síndrome de lipodistrofia, caracterizada por cambios morfológicos en la distribución de la grasa corporal y de los niveles metabólicos en los lípidos y glicidos séricos, creciendo el riesgo de enfermedades crónicas con impacto cardiovascular. Así, los tratamientos complementarios no medicados, como el entrenamiento de fuerza, son esenciales en el tratamiento de estos pacientes, lo que contribuye en las mejoras inmunometabólicas en esta población, lo que contribuye a hacer frente a la enfermedad. El propósito de esta investigación fue verificar la influencia de un protocolode entrenamiento de fuerza con duración de 12 semanas en los sistemas inmunometabólicos de personas con HIV/SIDA.Este es un estudio cuasi-experimental, realizado con 20 pacientes (16 hombres), todos con HIV/SIDA usando la terapia HAART,sometidos a un protocolo de entrenamiento de fuerza de 12 semanas. Se tomaron medidas de las variables número de célulasT CD4 +, niveles séricos de triglicéridos, colesterol (total y fracciones) y glucosa en sangre, antes y después del entrenamiento.Los datos fueron analizados mediante estadística descriptiva, con prueba T pareada y nivel significativo establecido en p <0,05.El resultado mostró un aumento significativo en las células T CD4 + en un 15,4% (p=0,009), aunque no es estadísticamentesignificativo, tuve la glucosa en sangre reducida, así como el colesterol total y los triglicéridos, con respectivo aumento dela fracción de colesterol HDL. Por lo tanto, sugerimos que el entrenamiento de fuerza puede ser efectivo en las condicionesinmunológicas y metabólicas de las personas que viven con HIV/AIDS, aumentando las células T CD4 + y controlando los...(AU)

Immune cell infiltration features and related marker genes in lung cancer based on single-cell RNA-seq

Purpose Immune cells in the immune microenvironment of lung cancer have a great impact on the development of lung cancer. Our purpose was to analyze the immune cell infiltration features and related marker genes for lung cancer. Methods Single cell RNA sequencing data of 11,485 lung cancer cells were retrieved from the Gene Expression Omnibus. After quality control and data normalization, cell clustering was performed using the Seurat package. Based on the marker genes of each cell type from the CellMarker database, each cell was divided into G1, G2M, and S phases. Then, differential expression and functional enrichment analyses were performed. CIBERSORT was used to reconstruct immune cell types. Results Following cell filtering, highly variable genes were identified for all cells. 14 cell types were clustered. Among them, CD4 + T cell, B cell, plasma cell, natural killer cell and cancer stem cell were the top five cell types. Up-regulated genes were mainly enriched in immune-related biological processes and pathways. Using CIBERSORT, we identified the significantly higher fractions of naïve B cell, memory CD4 + T cell, T follicular helper cell, T regulatory helper cell and M1 macrophage in lung cancer tissues compared to normal tissues. Furthermore, the fractions of resting NK cell, monocyte, M0 macrophage, resting mast cell, eosinophil and neutrophil were significantly lower in tumor tissues than normal tissues. Conclusion Our findings dissected the immune cell infiltration features and related marker genes for lung cancer, which might provide novel insights for the immunotherapy of lung cancer (AU)

Pulmonary sarcoidosis: prognostic factors at diagnosis in patients from North of Portugal / Sarcoidosis pulmonar: factores pronósticos en el diagnóstico en enfermos del norte de Portugal

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease that affects the lungs in more than 90% of the patients. It is associated with a variable clinical course and considering all the different forms of disease presentation, there are an absence of reliable clinical prognostic markers that can predict the outcome at diagnosis. OBJECTIVE: The aim of our study was to investigate prognostic factors at diagnosis in a population of sarcoidosis patients from Northern Portugal. METHODS: A group of 110 patients with chronic evolution was compared with 129 patients with disease resolution regarding their clinical, radiologic and laboratorial features. RESULTS: We found a positive association between the chronic forms and lung function impairment, radiologic stage II, lower lymphocyte CD4/CD8 and extrapulmonary disease. Löfgren syndrome and asthenia instead had a protective significant association to chronicity. Our final logistic regression model found a significant independent association between age (adjusted OR=1.06), extrapulmonary involvement (adjusted OR=2.68), Löfgren's syndrome (adjusted OR=0.15) with outcome toward chronicity. CONCLUSIONS: In this first study searching for prognostic factors at diagnosis in a Northern Portuguese population, we found clinical prognosis factors that have been described in other populations that should be considered whenever sarcoidosis is identified

INTRODUCCIÓN: La sarcoidosis es una enfermedad granulomatosa multisistémica que afecta a los pulmones en más del 90% de los enfermos. Está asociada a un curso clínico variable y, considerando todas las formas diferentes de presentación de la enfermedad, hay una ausencia de marcadores de pronóstico clínico confiables que puedan predecir el resultado en el momento del diagnóstico. OBJETIVO: El objetivo de nuestro estudio fue investigar los factores pronósticos en el momento del diagnóstico en una población de enfermos con sarcoidosis del norte de Portugal. MÉTODOS: Se comparó un grupo de 110 enfermos con evolución crónica con 129 enfermos con resolución de la enfermedad teniendo en cuenta sus características clínicas, radiológicas y de laboratorio. RESULTADOS: Se encontró una asociación positiva entre las formas crónicas y el deterioro de la función pulmonar, el estadio radiológico II, la relación CD4/CD8 más baja y la enfermedad extrapulmonar. Ya el síndrome de Löfgren y la astenia tuvieron una asociación protectora significativa con la cronicidad. Nuestro modelo de regresión logística final encontró una asociación independiente significativa entre la edad (OR ajustada=1,06), la afectación extrapulmonar (OR ajustada=2,68), el síndrome de Löfgren (OR ajustada=0,15) y el resultado hacia la cronicidad. CONCLUSIONES: En este primer estudio de búsqueda de factores pronósticos en el momento del diagnóstico en una población del norte de Portugal, fueron encontrados predictores clínicos, que se han descrito en otras poblaciones que se deben considerar cada vez que se hace el diagnóstico de una sarcoidosis

Tratamiento con pembrolizumab en paciente con infección por virus de la inmunodeficiencia humana y leucoencefalopatía multifocal progresiva / Pembrolizumab treatment for progressive multifocal leukoencephalopathy in a patient with Human Immunodeficiency Virus infection

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Fungal co-infection in COVID-19 patients: should we be concerned? / Coinfección fúngica en pacientes con COVID-19: ¿debemos preocuparnos?

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy

Los pacientes gravemente enfermos con COVID-19 presentan concentraciones más elevadas de citoquinas pro-inflamatorias (IL-1, IL-2, IL-6 y factor de necrosis tumoral alfa) y anti-inflamatorias (IL-4 e IL-10), menor expresión de interferón-gama y un número más bajo de células CD4 y CD8. Esta grave situación clínica aumenta el riesgo de padecer coinfecciones fúngicas, como la aspergilosis pulmonar invasora, la candidiasis invasora o la neumonía por Pneumocystis jirovecii. Sin embargo, pocos estudios han investigado las coinfecciones fúngicas en esta población. En esta revisión describimos una actualización de las publicaciones sobre coinfecciones fúngicas en esta población de pacientes y nuestra experiencia personal en tres hospitales españoles. Podemos concluir que a pesar de la grave enfermedad causada por el SARS-CoV-2 en muchos pacientes, la baja frecuencia de micosis invasoras se debe probablemente a las pocas broncoscopias y necropsias realizadas en estos pacientes debido al alto riesgo de producción de aerosoles. Sin embargo, la presencia de marcadores fúngicos en muestras clínicas relevantes, con la excepción de la colonización broncopulmonar por Candida, debería aconsejar la instauración precoz de una terapia antifúngica

Trastorno linfoproliferativo primario de células T pleomórficas pequeñas/medianas CD4+ coincidente en dos hermanas / Coincident Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoproliferative Disorder in Two Sisters

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Actividad inmunosupresora de la corteza de Bursera simaruba (L.) Sarg (Burseraceae) / Immunosuppressive activity of the bark of Bursera simaruba (L.) Sarg (Burseraceae) / Atividade imunossupressora da casca de Bursera simaruba (L.) Sarg (Burseraceae)

ANTECEDENTES: Un gran número de plantas medicinales han mostrado actividad inmunosupresora. Bursera simaruba, es un árbol comúnmente difundido en Colombia. En el país se ha utilizado tradicionalmente para el tratamiento de infecciones internas y externas. OBJETIVO: Investigar el efecto inmunomodulador de una infusión de la corteza de Bursera simaruba sobre los linfocitos T CD4+ y T CD8+ en humanos. MÉTODOS: Se reclutaron 10 participantes, se les explicó el procedimiento a seguir firmando el consentimiento informado. Se suministró una toma diaria de una infusión preparada con 5 g de la corteza de Bursera simaruba en 200 mL de agua. La actividad inmunomoduladora se estudió mediante el recuento de linfocitos T usando citometría de flujo. Los datos se analizaron estadísticamente con la prueba t-Student para muestras relacionadas. RESULTADOS: Un 90% de los participantes mostraron una disminución en los linfocitos T CD4+ (p = 0,024) y un 70% de los participantes mostraron una disminución en los linfocitos T CD8+ (p = 0,019), indicando una acción directa de la infusión sobre la población de linfocitos. CONCLUSIÓN: El extracto de la corteza de Bursera simaruba tiene efectos inmunosupresores y podría ser una opción terapéutica potencial en el trasplante de órganos, o en terapia antitumoral

BACKGROUND: A big number of medicinal plants have shown immunosuppressive activity. Bursera simaruba, is a tree commonly spread in Colombia. In the country it has been traditionally used for the treatment of internal and external infections. OBJECTIVE: To investigate the immunomodulatory effect of an infusion of Bursera simaruba bark on human CD4+ T and CD8+ T lymphocytes. METHODS: Ten participants were recruited, the procedure to continue signing informed consent was explained. A daily intake of an infusion prepared with 5 g of the bark of Bursera simaruba in 200 mL of water was supplied. Immunomodulated activity was studied by T lymphocyte count using flow cytometry. Data were statistically analyzed with the t-Student test for related samples. RESULTS: 90% of the participants showed a decrease in CD4+ T lymphocytes (p = 0.024) and 70% of the participants showed a decrease in CD8+ T lymphocytes (p = 0.019), indicating a direct action of the infusion on the population of lymphocytes. CONCLUSION: The bark extract of Bursera simaruba has immunosuppressive effects and could be a potential therapeutic option in organ transplantation, or antitumor therapy

ANTECEDENTES: Um grande número de plantas medicinais tem demonstrado atividade imunossupressora. Bursera simaruba, é uma árvore comumente disseminada na Colômbia. Neste país, tem sido tradicionalmente utilizada para o tratamento de infeções internas e externas. OBJETIVO: Investigar o efeito imunomodulador de uma infusão de casca de Bursera simaruba em linfócitos CD4+ T e CD8+ T humanos. MÉTODOS: Foram recrutados dez participantes, tendolhes sido explicado o procedimento a seguir, e sido assinada a declaração de consentimento informado. Foi fornecida para ingestão diária uma infusão preparada com 5 g da casca de Bursera simaruba em 200 mL de água. A atividade imunomoduladora foi estudada por contagem de linfócitos T usando citometria de fluxo. Os dados foram analisados estatisticamente com o teste t-Student para amostras relacionadas. RESULTADOS: 90% dos participantes apresentaram uma diminuição nos linfócitos T CD4+ (p = 0,024) e 70% dos participantes mostraram uma diminuição nos linfócitos T CD8+ (p = 0,019), indicando uma ação direta da infusão na população de linfócitos. CONCLUSÃO: O extrato da casca de Bursera simaruba tem efeitos imunossupressores e pode ser uma potencial opção terapêutica em casos de transplante de órgãos ou terapia antitumoral

Low percentages of regulatory T cells in common variable immunodeficiency (CVID) patients with autoimmune diseases and its association with increased numbers of CD4+CD45RO+ T and CD21low B cells

Background: Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies defined by marked reductions in serum IgG, IgA and/or IgM levels and recurrent bacterial infections. Some patients are associated with defects in T cells and regulatory T cells (Tregs), resulting in recurrent viral infections and early-onset autoimmune disease. Methods: We analyzed whether there is an association between Tregs cells (CD4+CD25+CD127low and CD4+CD25+FoxP3+); memory T cells (CD4+CD45RO+); memory B cells (CD19+CD27-IgD-); and CD21low B cells (CD19+CD38lowCD21low); as well as autoimmune manifestations in 36 patients with CVID (25 women and 11 men, mean age 24 years), all by flow cytometry. Results: Fourteen patients presented with autoimmune diseases (AI) (39%), including 11 with autoimmune thrombocytopenia (ITP) (31%); two with vitiligo (6%); one with systemic lupus erythematosus (LES) (3%); and one with multiple sclerosis (MS) (3%). CVID patients with AI had a reduced proportion of Tregs (both CD4+CD25+CD127low and FoxP3+ cells) compared with healthy controls. CVID patients with AI had expanded CD21low B cell populations compared with patients who did not have AI. A correlation between increased CD4+CD45RO T cell populations and reduced Tregs was also observed. Conclusions: Our results showed that 39% of patients with CVID had AI and reduced Tregs populations. Research in this area might provide noteworthy data to better understand immune dysfunction and dysregulation related to CVID

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IFN-γ stimulation of dental follicle mesenchymal stem cells modulates immune response of CD4+ T lymphocytes in Der p1+ asthmatic patients in vitro

Background: House dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4+ T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells. Objective: We aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-γ stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid. Material and methods: PBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-γ or Der p1 or Dexamethasone for 72h. CD4+ T proliferation, cell viability, CD4+CD25+FoxP3+ Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry. Results: DF-MSCs suppressed proliferation of CD4+ T lymphocytes (pCDmix < 0.01, pDerp1 < 0.01, pIFN < 0.005) by increasing the number of FoxP3 expressing CD4 + CD25 + T regulatory cells (pCDmix < 0.005, pDerp1 < 0.01, pIFN < 0.001) and suppressed lymphocyte apoptosis (pCDmix < 0.05, pDerp1< 0.05, pIFN < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-γ stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4+CD25 + T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (pCDmix < 0.01, pDerp1 < 0.05, pIFN < 0.05) and upregulating IFN-γ levels (pCDmix < 0.01, pDerp1< 0.05, pIFN < 0.005) in asthmatic patients. Conclusion: IFN-γ stimulated DF-MSCs were found to have a high modulatory effect on CD4 + T cell responses, while Dexamethasone had an apoptotic effect on CD4+ T cells in asthmatic patients. DF-MSCs may be a new cell-based therapy option for allergic diseases including asthma

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Effect of vitamin D3 supplementation on HIV-infected adults: a systematic reviewVitamin D? Supplementation on HIV-Infected Adults: A Systematic Review / Efecto de la suplementación con vitamina D3 en adultos infectados por el VIH: una revisión sistemática

Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections

Introducción: muchas evidencias ratifican que la vitamina D puede estar asociada con la mejora de los niveles de células CD4 en individuos infectados por el VIH, tratados con terapia antirretroviral (ART) que se asocia a la disminución de los niveles de 25(OH)D. Objetivo: realizar una revisión sistemática sobre el efecto de la suplementación de vitamina D en pacientes adultos infectados con VIH. Métodos: la investigación fue realizada en las bases de datos Science Direct, PubMed, BVS, Scielo Cochrane y periódicos, de febrero a abril de 2018, con límite de publicación de 2000 a 2018, sin restricción de género, etnicidad y que involucra a individuos con edad mayores de 18 años. Para la evaluación de la calidad de los estudios, se utilizó el protocolo Preferred Reporting Items for Systematic Reviews y Meta-Analyzes (PRISMA) y la escala de Jadad. Resultados: la encuesta inicialmente resultó en 198 artículos. Después del proceso de selección, 5 artículos fueron identificados como elegibles, donde ponen de manifiesto que la suplementación con vitamina D puede ser una intervención asociada y eficaz para reducir la hipovitaminosis. La ART reduce niveles de la vitamina D3 y altera su metabolismo, estando asociada al riesgo de mortalidad. Sin embargo, los niveles adecuados de 25(OH)D están asociados positivamente al número de células CD4 + y la reducción de los niveles de infecciones. Conclusión: la suplementación de vitamina D promueve la recuperación inmunológica. Sin embargo, los casos analizados fueron pocos, insuficientes para confirmar totalmente los beneficios y recomendar la suplementación. Por lo tanto, estudios de intervención son necesarios para elucidar la actuación de la vitamina D en la protección humana contra las infecciones por el VIH

l-Thyroxine does not prevent immunemediated sensorineural hearing loss in autoimmune thyroid diseases / l-Tiroxina no previene la hipoacusia neurosensorial inmuno-mediada en enfermedades tiroideas autoinmunes

Objective: This is the first report dealing with immune-mediated inner ear disease (IMIED) hearing loss in a group of patients affected with autoimmune thyroid disease (AITD), whose treatment required corticosteroids, despite being treated with levothyroxine. Immunopathology linking the inner ear and the thyroid gland is also presented. Patients: A total of 220 patients were selected with sensorineural hearing loss (SNHL) of causes other than presbycusis. Audiometry was performed and pure tone average was calculated before and after treatment with corticosteroids. Results: Eighty-four (84) patients had SNHL of autoimmune origin, and 15 patients were diagnosed with AITD (Hashimoto's disease). Bilateral hearing loss was observed in 10 patients (66.5%). Sudden sensorineural hearing loss was the most frequent clinical form of presentation. Nine patients showed a hearing recovery greater than 10 dB after corticosteroid treatment. Conclusions: Acquired hypothyroidism is thought to affect hearing due to different mechanisms. Although specific hormonal therapy may improve peripheral or central auditory disorders associated with hypothyroidism, the presence of IMIED in AITD patients requires another approach. Altered immune regulatory mechanisms involving Treg cells and CD4+CD45RO cells have been suggested in patients with AITD and IMIED. In the present study, although all the patients with hypothyroidism and subclinical hypothyroidism were being treated with levothyroxine, immune-mediated hearing loss was observed. Therapy with corticosteroids could achieve hearing recovery. Since inner ear and thyroid gland share possible antigen targets, we highlight the existence of IMIED in AITD patients and the importance of implementing appropriate therapy with corticosteroids

Objetivo: Este es el primer trabajo que trata la hipoacusia por enfermedad inmune-mediada del oído interno (IMIED) en un grupo de pacientes afectados de tiroiditis autoinmune (AITD), cuyo tratamiento requirió corticosteroides, a pesar de haber sido tratados con levotiroxina. También se presenta la inmunopatología que vincula el oído interno y la glándula tiroides. Pacientes: Se seleccionó un total de 220 pacientes con hipoacusia neurosensorial (SNHL) por causas diferentes a presbiacusia. A todos los pacientes se les realizó una audiometría, calculándose la media de tonos puros antes y después del tratamiento con corticosteroides. Resultados: Ochenta y cuatro (84) pacientes tenían SNHL de origen autoinmune, y 15 pacientes fueron diagnosticados de AITD (Enfermedad de Hashimoto). Se observó hipoacusia bilateral en 10 pacientes (66,5%). La sordera súbita fue la forma de presentación clínica más frecuente. Nueve pacientes presentaron una recuperación auditiva superior a 10 dB tras el tratamiento con corticosteroides. Conclusiones: Se piensa que el hipotiroidismo adquirido afecta a la audición por diferentes mecanismos. Aunque la terapia hormonal específica puede mejorar los trastornos auditivos periféricos o centrales asociados al hipotiroidismo, la presencia de IMIED en los pacientes de AITD requiere otro abordaje. Se ha sugerido una alteración de los mecanismos reguladores de la respuesta inmune que implica a las células de Treg y a las células CD4+CD45RO en los pacientes con AITD e IMIED. En el presente estudio, a pesar de que todos los pacientes con hipotiroidismo e hipotiroidismo subclínico estaban siendo tratados con levotiroxina, se observó hipoacusia inmuno-mediada. La terapia con corticosteroides podría lograr una recuperación auditiva. Dado que el oído interno y la glándula tiroides comparten posibles antígenos diana, destacamos la existencia de IMIED en los pacientes de AITD, y la instauración de una terapia adecuada con corticosteroides

The profile of IL-4, IL-5, IL-10 and GATA3 in patients with LRBA deficiency and CVID with no known monogenic disease: Association with disease severity

Background: Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like anchor protein (LRBA) deficiency is an autosomal recessive disease characterized by a CVID-like phenotype. T cell abnormality was reported in patients with CVID and LRBA deficiency. The study's aim was to evaluate IL-4, IL-5, IL-10 and GATA3 expression in patients with LRBA deficiency and CVID with no known monogenic disease, and further evaluate its relevance with immunological futures and clinical complications of patients. Methods: The study population comprised patients with CVID, LRBA deficiency and age-sex matched healthy controls. Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of mentioned cytokines was assessed by enzyme-linked immunosorbent assay. Results: The main clinical presentations of CVID patients were infections only and lymphoproliferations phenotypes, but in LRBA patients were autoimmune and enteropathy phenotype. The frequencies of CD4+ T cells were significantly reduced in LRBA and CVID patients. There were no statistically significant differences among GATA3, IL4, and IL5 gene expressions by CD4+ T cells of patients and controls, however, the IL10 expressions in CVID patients was significantly lower than in LRBA patients and HCs. As compared with HCs, CVID patients showed a prominent decrease in IL-4 and IL-10 production by CD4+ T cells. Conclusions: Our findings demonstrated that patients with CVID and LRBA deficiency (even with severe infectious and inflammatory complications) have not imbalance in Th2 response, which is in parallel with lower frequency of allergy and asthma in these patients

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"Supersoldados T" contra el cáncer: inmunoterapia con receptores de antígeno quimérico (o CAR) / No disponible

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CTLA-4 expression in CD4+ T cells from patients with LRBA deficiency and common variable immunodeficiency with no known monogenic disease

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Ecografía del síndrome linfoproliferativo primario cutáneo T CD4+ de célula pequeña/mediana / Ultrasound Appearance of Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder

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Placas eritematosas infiltradas como presentación de un linfoma de rápida evolución / Erythematous infiltrated plaques as an onset manifestation of rapidly evolving lymphoma

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