Protocol to desensitize human and murine mast cells after polyclonal IgE sensitization.

In this protocol, we provide detailed instructions to desensitize human and murine mast cells (MCs) after polyclonal IgE sensitization. Moreover, we specify the steps for MC degranulation assessment after desensitization, measuring CD63 and CD107a expression by flow cytometry and b-hexosaminidase activity. Desensitized MCs can be used directly for co-culture with other cell types, immunofluorescence, live imaging, and omics approaches.post-print3350 K

Local inflammation enables a basophil-neuronal circuITCH in atopic dermatitis.

post-print1573 K

El flamenco como vehículo comunicativo entre culturas: La imagen del flamenco en la prensa japonesa.

España y Japón son dos países separados por 10.642 kilómetros que poseen un sinfín de diferencias como su lenguaje, sus costumbres o su entorno. Sin embargo, la pasión de la población japonesa por uno de los bienes culturales españoles más conocidos, el flamenco, es latente desde años antes de la dictadura franquista. Este estudio trata de conocer las relaciones entre España y Japón gracias al flamenco y de estudiar cuál es la verdadera relevancia que posee este bien cultural español en el país nipón. Para ello, se va a analizar qué importancia otorga la prensa digital japonesa al flamenco a través de su contenido. <br /

Abordaje fisioterápico en una niña con síndrome de Angelman: a propósito de un caso

Introducción. El síndrome de Angelman es un trastorno del neurodesarrollo que se caracteriza por un retraso psicomotor acompañado de trastornos en el movimiento, un profundo retraso cognitivo con graves dificultades de aprendizaje, habla muy limitada, conducta hiperactiva y risa frecuente, producida por una alteración genética en el que se ve involucrado un cromosoma materno. Objetivos. Los objetivos se centran en estimular el desarrollo psicomotor tratando de conseguir la máxima independencia, evitando a su vez la aparición de deformidades, ayudándose del uso de dispositivos ortopédicos. Metodología. Se aplica un diseño AB longitudinal prospectivo. El sujeto de estudio es una niña de 4 años de edad, diagnosticado de síndrome de Angelman, que se manifiesta clínicamente con retraso psicomotor, inestabilidad en el equilibrio estático y dinámico y alteraciones ortopédicas, afectando a su autonomía. Se realiza una valoración fisioterápica inicial para la consiguiente elaboración del plan de intervención fisioterápico, utilizando distintos dispositivos ortopédicos. Desarrollo. Se aplica el tratamiento fisioterápico 3 veces por semana durante 6 meses, observándose en los resultados de la valoración final una mejoría a nivel motor y cognitivo junto con una mayor autonomía. Conclusiones. A pesar de que los resultados no son generalizables, el plan de intervención fisioterápico propuesto muestra mejoras en la evolución de la paciente, aunque sería conveniente hacer más estudios para encontrar evidencia de otras vías de tratamiento, dado que es un síndrome poco frecuente. Palabras clave: síndrome de Angelman, hiperactividad, dispositivos ortopédicos

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).Severo Ochoa Center of Excellence, Grant/Award Number: CEX2020-001041- S; Pro CNIC Foundation; Ministerio de Ciencia e Innovación; Ministry of Science and Innovation, Grant/ Award Number: PID2019-110369RB- I00; European Commission, Grant/Award Number: ERC-CoG 819775 and H2020-HEALTH 945118; Spanish Ministry of Universities; Ayudas Margarita Salas para la Formación de Jóvenes Doctores—Universidad Autónoma de Madrid, Grant/ Award Number: CA1/RSUE/2021–00577; Formación de Profesorado Universitario, Grant/Award Number: FPU16/03953; Sociedad Española de Alergología e Inmunología Clínica (SEAIC), Grant/ Award Number: BECA20A9; New Frontiers in Research Fund, Grant/ Award Number: NFRFE-2019- 00083; The Nutricia Research Foundation, Grant/Award Number: NRF-2021- 13; Instituto de Salud Carlos III, Grant/Award Number: PI21/00158, PI21/01126, CP20/00043, PI18/01467, PI19/00044, RD16/0006/0015 and RD21/0002/0008; Severo Ochoa Program, Grant/Award Number: AEI/SEV-2017- 0712S

Amyloid β / PKC-dependent alterations in NMDA receptor composition are detected in early stages of Alzheimer´s disease

[EN] Amyloid beta (Abeta)-mediated synapse dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Abeta peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in the early stages of AD are unclear. Here, we observed that NMDAR subunit NR2B and PSD-95 levels were aberrantly upregulated and correlated with Abeta42 load in human postsynaptic fractions of the prefrontal cortex in early stages of AD patients, as well as in the hippocampus of 3xTg-AD mice. Importantly, NR2B and PSD95 dysregulation was revealed by an increased expression of both proteins in Abeta-injected mouse hippocampi. In cultured neurons, Abeta oligomers increased the NR2B-containing NMDAR density in neuronal membranes and the NMDA-induced intracellular Ca2+ increase, in addition to colocalization in dendrites of NR2B subunit and PSD95. Mechanistically, Abeta oligomers required integrin beta1 to promote synaptic location and function of NR2B-containing NMDARs and PSD95 by phosphorylation through classic PKCs. These results provide evidence that Abeta oligomers modify the contribution of NR2B to NMDAR composition and function in the early stages of AD through an integrin beta1 and PKC-dependent pathway. These data reveal a novel role of Abeta oligomers in synaptic dysfunction that may be relevant to early-stage AD pathogenesis.We thank S. Marcos, L. Escobar, A Martínez and Z. Martínez for technical assistance. This study was supported by the Basque Government (IT1203-19; PIBA_2020_1_0012; ELKARTEK KK-2020/00034; fellowship to T.Q-L, U.B. and J.Z-I), University of the Basque Country (UPV/EHU; fellowship to C.O-S) CIBERNED, MICINN (PID2019-108465RB-I00) and Fundación Tatiana Pérez de Guzmán el Bueno (fellowship to C.L)

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).N

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56–CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic interventionThe study was funded by grants SAF2017- 82886-R to FS-M from the Ministerio de Economía y Competitividad, and from “La Caixa Banking Foundation” (HR17-00016) to FS-M. Grant PI018/01163 to CMC and grant PI19/00549 to AA were funded by Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain. SAF2017-82886-R, PI018/01163 and PI19/00549 grants were also co-funded by European Regional Development Fund, ERDF/FEDER. This work has been funded by grants Fondo Supera COVID (CRUE-Banco de Santander) to FSM, and “Ayuda Covid 2019” from Comunidad de Madri

Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH

El objetivo de este documento es actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el VIH del año 2010. La función renal debe monitorizarse en todos los pacientes e incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación CKD-EPI), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. También se revisan las indicaciones de la biopsia renal, cuándo enviar el paciente al nefrólogo y las indicaciones, evaluación y manejo del paciente en diálisis o del trasplante renal

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.We thank Dr. A. Egui, Dr A. Fernández-Villegas and A. López-Barajas from IPBLNsingle bondCSIC (Granada, Spain), Carme Subirá from ISGlobal (Barcelona, Spain), and Suelene B. N. Tavares from Hospital das Clínicas (Goiás, Brazil) for their technical assistance. We also want to thank Dr. B. Carrilero from Hospital Virgen de la Arrixaca (Murcia, Spain), Dr. Dayse E.C. de Oliveira from Hospital das Clínicas (Goiás, Brazil), and Dr. Raúl Chadi from Hospital General de Agudos “Dr. I. Pirovano” for their clinical follow up of patients. ISGlobal authors thanks the support by the Departament d'Universitats i Recerca de la Generalitat de Catalunya, Spain (AGAUR; 2017SGR00924), funding by the Instituto de Salud Carlos III project PI18/01054 and RICET Network for Cooperative Research in Tropical Diseases (RD12/0018/0010) and FEDER, and the support to ISGlobal from the Spanish Ministry of Science Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023″ Program (CEX2018–000806-S), and from the Generalitat de Catalunya through the CERCA Program. IPBLN work was financially supported by grants SAF2016–81003-R and SAF2016–80998-R from the Programa Estatal I + D + i (MINECO) and ISCIII RICET (RD16/0027/0005) and FEDER. MJP research is supported by the Ministry of Health, Government of Catalunya (PERIS 2016–2010 SLT008/18/00132). TAJ thanks the support of Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq/ 313011/2018–4) and Fundação Oswaldo Cruz/MS (25380.001603/2017–89). Authors also thank Drugs for Neglected Diseases initiative and Fundacion Mundo Sano for financial support. For this project, DNDi received financial support from the following donors: UK Aid, UK; Directorate-General for International Cooperation (DGIS), The Netherlands; Swiss Agency for Development and Cooperation (SDC), Switzerland; Médecins Sans Frontières (MSF), International. The donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript