RESUMEN

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

Asunto(s)

RESUMEN

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

RESUMEN

Ethanol use during pregnancy is a risk factor for developing adverse outcomes. Its metabolism by cytochrome P450 2E1 (CYP2E1) produces radical oxygen species (ROS), promoting cellular injury and apoptosis. To date, no studies have been conducted to elucidate the teratogenic effects due to both IGF-1 deficiency and ethanol consumption in mice placentas. The aim of this study is to determine the effect of ethanol consumption on the placenta and liver of partially IGF-1-deficient mice, the role of metabolism via CYP2E1, and the antioxidant enzyme system. Heterozygous (HZ, Igf1+/-) pregnant female mice were given water or 10% ethanol. Wild-type (WT, Igf1+/+) female mice were used as controls. At gestational day 19, pregnant dams were euthanized, and maternal liver and placentas were collected. Pregnant HZ dams were smaller than controls, and this effect was higher due to ethanol consumption. Cyp2e1 gene was overexpressed in the liver of HZ pregnant dams exposed to ethanol; at the protein level, CYP2E1 is reduced in placentas from all genotypes. The antioxidant enzymatic system was altered by ethanol consumption in both the maternal liver and placenta. The results in this work hint that IGF-1 is involved in intrauterine development because its deficiency exacerbates ethanol's effects on both metabolism and the placenta.

RESUMEN

Cells sense and respond to a variety of physical cues from their surrounding microenvironment, and these are interpreted through mechanotransductive processes to inform their behavior. These mechanisms have particular relevance to stem cells, where control of stem cell proliferation, potency, and differentiation is key to their successful application in regenerative medicine. It is increasingly recognized that surface micro- and nanotopographies influence stem cell behavior and may represent a powerful tool with which to direct the morphology and fate of stem cells. Current progress toward this goal has been driven by combined advances in fabrication technologies and cell biology. Here, the capacity to generate precisely defined micro- and nanoscale topographies has facilitated the studies that provide knowledge of the mechanotransducive processes that govern the cellular response as well as knowledge of the specific features that can drive cells toward a defined differentiation outcome. However, the path forward is not fully defined, and the "bumpy road" that lays ahead must be crossed before the full potential of these approaches can be fully exploited. This review focuses on the challenges and opportunities in applying micro- and nanotopographies to dictate stem cell fate for regenerative medicine. Here, key techniques used to produce topographic features are reviewed, such as photolithography, block copolymer lithography, electron beam lithography, nanoimprint lithography, soft lithography, scanning probe lithography, colloidal lithography, electrospinning, and surface roughening, alongside their advantages and disadvantages. The biological impacts of surface topographies are then discussed, including the current understanding of the mechanotransductive mechanisms by which these cues are interpreted by the cells, as well as the specific effects of surface topographies on cell differentiation and fate. Finally, considerations in translating these technologies and their future prospects are evaluated.

RESUMEN

Previous research has indicated that many European buildings are vulnerable to moderate-magnitude earthquakes. For example, during the L´Aquila (Italia, Mw 6.3, 2009) and Lorca (Spain, Mw 5.9, 2011) earthquakes, many old buildings were severely damaged and some of them collapsed. In specific, significant damage has been found in several school buildings after past earthquakes in Europe. This is due to the fact that many of them were constructed prior to the current seismic codes, thus considering only gravitational loads and with no seismic design whatsoever. Primary schools are even more vulnerable than other typologies because of their low adult/child ratio. The seismic activity of the Iberian Peninsula is low-moderate. However, the Algarve and Huelva regions, which are situated in the south-west, are influenced by large faults which have caused major earthquakes of long-return periods. The European project PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) aims to cooperatively evaluate the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain) regions. The present work is framed under this project. The objective of this paper is to determine the most effective retrofitting scheme for a typical primary school building in this area, considering structural, architectural and constructive parameters. The scheme could be applied to several buildings of the same typology, decreasing costs and time. An existing reinforced concrete frame building has been selected for the study. This is one of the most commonly used typologies for primary schools in this area. A nonlinear static analysis has been carried out in order to study its seismic behaviour. The performance point of the building has been obtained through the capacity-demand spectrum method. The preliminary results have confirmed the poor seismic behaviour of this building. Specifically, soft-story behaviour has been identified in the ground floor and short columns have been observed in the upper floors. Therefore, specific seismic retrofitting solutions have been proposed and evaluated in order to identify the one that is the most efficient. The combination of reinforcements has been done considering the structural and architectural impact and constructive parameters. The calculations have shown that steel X-bracings are the best solution for preventing the formation of a soft-storey in the ground floor. Unfortunately, this scheme increases the deformation in the upper floor columns. The best solution for the upper floors' short columns has been the use of steel jackets. The results have also shown that this combination produces an important reduction of the expected general damage level. The resulting retrofitting scheme can be extrapolated to other buildings with a similar typology.

Asunto(s)

RESUMEN

BACKGROUND: Nasal hyperreactivity (NHR) is a common feature of various rhinitis subtypes and represents a novel phenotype of rhinitis. It is being reported in two-thirds of adult rhinitis patients irrespective of the atopic status. Data on the prevalence of NHR in patients with asthma are lacking, as well as the nature of evoking triggers. METHODS: Postal questionnaires were distributed to an unselected group of asthmatic patients in Leuven (Belgium, n = 190) and completed by 114 patients. In Mexico City (Mexico) and Brasov (Romania), respectively, 97 out of 110 and 80 out of 100 asthmatic patients attending the outpatient clinic completed the questionnaire. Non-asthmatic volunteers were recruited amongst university and hospital co-workers in Leuven (n = 53). The presence of self-reported NHR, the type of triggers evoking nasal and bronchial symptoms, medication use, self-reported allergy, and environmental factors were evaluated. RESULTS: Overall, 69% of asthma patients reported NHR, with 32% having more than 4 triggers evoking NHR. These triggers included mainly exposure to temperature and humidity changes, cigarette smoke, and strong odours. A higher prevalence of NHR was detected in allergic compared to non-allergic asthma patients (73% vs. 53% p < 0.01). The prevalence of NHR correlated with asthma severity, ranging from 63% (VAS ≤3) to 81% (VAS ≥7). BHR was found more frequently in patients with NHR compared to without NHR (89% vs. 53%, p < 0.0001). CONCLUSION: NHR represents a clinical phenotype of upper airway disease affecting over two-thirds of asthma patients and correlates with asthma severity. Targeting NHR in patients with asthma is often overlooked and should be reinforced in the future to achieve better symptom control.

RESUMEN

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Asunto(s)

RESUMEN

No disponible

Asunto(s)

RESUMEN

This paper aims to study different seismic retrofitting techniques to test the reduction of the seismic vulnerability of unreinforced masonry buildings. Three techniques have been considered in a case study: adding steel or carbon fibre reinforced polymer grids in the walls and steel encirclements in the openings. The performance-based method has been used to that purpose. Nonlinear static analyses have been performed to obtain the capacity and fragility curves, the performance point and the damage level states. Moreover, an analysis of the cost-benefit ratio has been carried out. Results have shown that the three techniques have produced considerable improvements. The addition of encirclements has reduced the deformation resulting in a slight increase of the structure's stiffness. Adding steel grids has produced the maximum peak strength increase while adding polymer grids has produced the largest ultimate displacements. Adding encirclement has had the best cost-benefit ratio.

Asunto(s)

Asunto(s)

RESUMEN

Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used.

Aunque existen guías clínicas de alta calidad sobre rinitis alérgica, numerosos pacientes reciben tratamiento deficiente, en parte debido al alto grado de automedicación. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS; en ella, los pacientes indican diariamente cuánto les molestan los síntomas a través de cinco pantallas con una escala visual análoga; recientemente se agregaron dos pantallas más (afectación del sueño). La aplicación también permite descargar los datos del "Diario de alergias" en la computadora del médico en el momento de la consulta a través de un código QR. En este artículo reseñamos el primer año de experiencia en España, México y Argentina, que utilizan la versión española.

Asunto(s)

RESUMEN

A project named PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) is being developed. It aims to cooperatively assess and improve the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain). A large number of schools have to be analysed. In order to determine which seismic retrofitting technique is optimal, an index-based method is presented in this paper. It considers three parameters: first, the efficiency of the seismic retrofitting technique in relation to the structural improvement obtained; second, the cost of the implementation of the retrofitting technique; and third, the architectural impact. It should be mentioned that a specific measurement for each solution according to its geometry has been performed. Also, coefficients to consider the singularities of each analysis and the importance of the parameters (number of buildings, typology, available funds, etc.) in the study are considered. The most representative primary school of Huelva has been chosen to test the index-based method. The most suitable retrofitting techniques for this type of buildings have been tested. The retrofitting technique which most increased the seismic performance has been the addition of X and V bracings within the building's bays. Furthermore, the analyses have revealed that adding the retrofitting elements in the most vulnerable direction of the building provides a high efficiency. The results have also shown that implementing techniques of lower architectural impact gives acceptable results. The analysis of the mean damage level index has shown that the building would experiment a severe damage. All the retrofitting techniques applied have reduced it, at least, up to moderate damage. Finally, it should be noted that the position of the retrofitting elements is also paramount for providing an optimal retrofitting.

Asunto(s)

RESUMEN

The vast majority of patients with allergic rhinitis (AR) do not receive the proper management which is recommended by the guidelines, but they frequently self-medicate. MASK (Mobile Airways Sentinel Network) is an integral part of a project that is supported by the European Union against chronic diseases and focused on active and healthy aging. MASK represents the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma), in which, by using a mobile application in a smart device, the objective is to guide the patient in the control of his/her multi-morbidity, AR and/or allergic conjunctivitis (AC) and/or asthma. The mobile app Allergy Diary by MACVIA-ARIA is free and it is available for both Android and iOS platforms. After it is downloaded to the patient's cell phone, it first requests some information about the patient's profile, allergic pathologies and medication; afterwards, through a visual analog scale, the patient is invited to determine the degree of affectation in the nose, eyes, and bronchi, and its influence on their productivity at work / school. After analyzing the data generated by filling the Allergy Diary, it became clear there is a new clinical entity: allergic rhinitis+ allergic conjunctivitis +asthma, with greater effect; in addition to a high level of self-medication: in general, the patient takes medication on days when symptoms are present. The app has already been deployed in 23 countries, including several Spanish-speaking countries.

La mayoría de los pacientes con rinitis alérgica no recibe el manejo idóneo, sino que se automedica. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS. Al descargarla al celular del paciente, a este se le piden datos de su perfil, patologías alérgicas y medicación; posteriormente, mediante una escala visual analógica se le invita a determinar el grado de afectación en nariz, ojos y bronquios y su influencia sobre su productividad laboral/escolar. Con los datos del Diario de Alergia se observa que existe un nuevo patrón de presentación: rinitis alérgica + conjuntivitis alérgica + asma, con mayor afectación, así como un alto nivel de automedicación: en general, el paciente toma medicación cuando presenta síntomas. La app se ha desplegado en 23 países, incluyendo varios países hispanohablantes.

Asunto(s)

RESUMEN

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

Asunto(s)

RESUMEN

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative.

RESUMEN

Para facilitar el aprendizaje de los estudiantes de medicina en el tema sangre, se confeccionó un software educativo de fácil navegabilidad, denominado SangreSoft, que permite enlazar textos, imágenes y videos, propicia mayor motivación para el estudio independiente, así como también para la asimilación, sistematización e integración de los contenidos, a la vez que contribuye al uso de la computación como medio de enseñanza. Este se elaboró en forma de página web, con lenguaje html, para lo cual se utilizó el Dreamweaver 8.0 como editor y el Internet Explorer 6.0 como visualizador. Se caracteriza por ser sencillo, no demanda de grandes conocimientos informáticos por parte del usuario y puede implementarse con relativa facilidad en los laboratorios docentes, con poco requerimiento tecnológico(AU)

To facilitate the learning for the medicine students about the topic blood, an educational software of easy navigability, denominated SangreSoft, was implemented, which allows to connect texts, images and videos, facilitates greater motivation for the independent study, as well as for the assimilation, systematization and integration of the contents, at the same time it contributes to the use of the computer science as a mean of teaching. This was elaborated as a web page, with language html, for which the Dreamweaver 8.0 was used as editor, and the Internet Explorer 6.0 as viewer. It is characterized for being simple, it doesn't demand of great computer knowledge by the user and it can be implemented with relative easiness in the teaching laboratories, with little technological requirement(AU)

Asunto(s)

RESUMEN

Avocado fruit extracts are known to exhibit antimicrobial properties. However, the effects on bacterial endospores and the identity of antimicrobial compounds have not been fully elucidated. In this study, avocado seed extracts were tested against Clostridium sporogenes vegetative cells and active endospores. Bioassay-guided purification of a crude extract based on inhibitory properties linked antimicrobial action to six lipid derivatives from the family of acetogenin compounds. Two new structures and four compounds known to exist in nature were identified as responsible for the activity. Structurally, most potent molecules shared features of an acetyl moiety and a trans-enone group. All extracts produced inhibition zones on vegetative cells and active endospores. Minimum inhibitory concentrations (MIC) of isolated molecules ranged from 7.8 to 15.6 µg/mL, and bactericidal effects were observed for an enriched fraction at 19.5 µg/mL. Identified molecules showed potential as natural alternatives to additives and antibiotics used by the food and pharmaceutical industries to inhibit Gram-positive spore-forming bacteria.

Asunto(s)

RESUMEN

Rhinosinusitis is a feature of aspirin-exacerbated respiratory disease (AERD), which in the initial phase is manifested as nasal congestion, mostly affecting females at the age of around 30 years on average. Subsequently, nasal inflammation progresses to chronic eosinophilic rhinosinusitis, asthma, nasal polyposis, and intolerance to aspirin and to other NSAIDs. While it has been long established that NSAIDs cause inhibition of cyclooxygenase-1 (COX-1), leading to excessive metabolism of arachidonic acid (AA) to cysteinyl-leukotrienes (cys-LTs), there is now evidence that both cytokines and staphylococcus superantigens amplify the inflammatory process exacerbating the disease. This paper gives a brief overview of the development of chronic rhinosinusitis (CRS) in sensitive patients, and we share our experience in the diagnosis and management of CRS in AERD.

Asunto(s)

RESUMEN

In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA(+)CCR7(-) phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells.

Asunto(s)