Modulation of the Serum Cytokine Expression Pattern in Hymenoptera Allergic Patients Treated with Specific Venom Immunotherapy

[EN] Venom immunotherapy (VIT) is an adequate model to explore the immune mechanisms underlying this type of treatment. We have investigated the use of protein arrays to detect variations in the levels of cytokines in patients receiving VIT. In the present study we selected 11 non-atopic patients with systemic reactions after Hymenoptera sting that received VIT during at least three years. In order to evaluate the success of VIT all of them should have tolerated a sting field after VIT. Serum samples were obtained before initiating VIT and after at least three years of successful VIT. We analyzed 42 serum proteins corresponding to a Th1/Th2 panel using protein array methodology. We observed a significant increase of Interleukin 10, Myeloid Macrophage Colony Stimulation Factor, Macrophage Derived Chemokine, Interleukin 1-α, Vascular Endothelial Growing Factor and Stem Cell Factor serum levels after successful VIT. We discuss the usefulness and normalization of this array method to analyze cytokines and other serum proteins. Monitoring these serum cytokines could help to predict the response and to elucidate the mechanisms underlying immunotherapy.Fundación para la Investigación de la Sociedad Española de Alergología e Inmunología Clínic

Polymorphisms of the IL12B, IL1B, and TNFA genes and susceptibility to asthma.

[EN] Asthma is one of the most common chronic inflammatory diseases in developed countries. Susceptibility to asthma is associated with interaction between multiple genes and environmental factors. Several cytokines play a major role in the pathophysiology of the disease. We analyzed the distribution of cytokine gene polymorphisms in a group of patients with asthma and a control group in order to determine the effect of these variants, or their combinations, on the development of clinical phenotypes. We genotyped 22 single-nucleotide polymorphisms (SNPs) corresponding to 13 cytokine genes (IFNG, IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, TGFB1, and TNFA) in 376 individuals (219 asthmatic patients and 157 controls). Genetic association was evaluated using genotype and allele models for different asthma phenotypes. Gene-gene interactions were explored using multifactor dimensionality reduction. Genotype AC of IL12B-1188 was associated with the presence of asthma. A significant association was detected between 2 SNPs analyzed in TNFA (-308 and -238) and atopic asthma and severe-persistent asthma. The IL1B TT haplotype (3962T and -511T) was also associated with atopy and moderate-persistent asthma. Our data show that the presence of SNPs in IL12B, TNFA, and IL1B was significantly associated with asthma, atopy, and severity of asthma.We also highlight the importance of genetic context, haplotype, and gene-gene interaction analysis in genetic association studies.Spanish Fondo de Investigación Sanitaria; Junta de Castilla y León; Foundation of the Spanish Society of Allergology and Clinical Immunology

Aplicación didáctica sistema solar en la asignatura de Ciencias Naturales, grupo 8vo grado del Instituto Héroes y Mártires Pueblo Nuevo en el primer semestre de 2019

En el presente trabajo de investigación se estudió la aplicación didáctica sistema solar en la asignatura de Ciencias Naturales, grupo 8vº grado del Instituto Héroes y Mártires Pueblo Nuevo en el primer semestre de 2019, con el fin de diseñar nuevas estrategias de aprendizaje y evaluación en el proceso de enseñanza -aprendizaje de la unidad didáctica “sistema solar”, de la disciplina referida en educación secundaria. Se evidenció la aplicación de nuevas habilidades de instrucción y evaluación para mejorar el proceso de enseñanza –aprendizaje entre el estudiantado, mismas que lleven a estos a una instrucción significativa, partiendo de los conocimientos previos del mismo a la construcción de un nuevo discernimiento desde la praxis, convirtiéndose así en un adiestramiento para la vida. La contribución teórica de este estudio comprende una amplia revisión bibliográfica sobre unidad didáctica y estrategias de aprendizaje; en tanto, el aporte práctico es la elaboración de un compendio metodológico para estimular la cognición en los colegiales en la modalidad de secundaria, así como en la disciplina mencionada con anterioridad. También ha fortalecido las capacidades docentes y, por ende, mejorará la calidad educativa, en el contexto en donde se desempeñan los autores. En definitiva, el impulso de la disertación es crear nuevos conocimientos, y proponer alternativas a la problemática pedagógica particular aquí expuesta

PTGDR gene in asthma: a functional, genetic, and epigenetic study.

[EN] Asthma affects more than 300 million individuals in the world. Several studies have demonstrated the importance of the genetic component. The aim of this study is to develop a holistic approach, including genetic, epigenetic, and expression analysis to study the Prostaglandin D2 receptor gene (PTGDR) in asthmatic patients. In this study, 637 Caucasian individuals were included. Genetic variants were characterized by sequencing, and haplotype and diplotype combinations were established. Electrophoretic mobility shift assays (EMSAs) were performed with different promoter variants. An epigenetic analysis of PTGDR was for the first time developed by MassArray assays, and gene expression was determined by real-time polymerase chain reaction. The -197T > C (Fisher's P = 0.028) and -613C > T (Fisher's P T SNP determined variations in the EMSAs. Moreover, consistent differences in the methylation and expression patterns were observed between asthmatic patients and controls determining a 2.34-fold increase of PTGDR gene expression in asthmatic patients. Genetic combinations described have functional implications in the PTGDR promoter activity by changing the transcription factors affinity that will help characterize different risk groups. The differences observed in the transcription factors affinity and in the methylation pattern bring insight into different transcription regulation in these patients. To the best of our knowledge, this is the first work in which the implication of genetic and epigenetic factors of PTGDR has been characterized pointing to putative therapeutic targets.Spanish Fondo de Investigación Sanitaria (FIS); Junta de Castilla y Leó

Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population

[EN] Background: Several null-mutations in the FLG gene that produce a decrease or absence of filaggrin in the skin and predispose to atopic dermatitis and ichthyosis vulgaris have been described. The relationship with asthma is less clear and may be due to the influence of atopy in patients with associated asthma. Methods: Four hundred individuals were included, 300 patients diagnosed with asthma divided into two groups according to their phenotype (allergic and non-allergic asthma) and 100 strictly characterized controls. The coding region and flanking regions of the FLG gene were amplified by PCR. We proceeded to the characterization of potential gene variants in that region by RFLP and sequencing and analysed their association with lung function parameters, asthma control and severity, and quality of life. Results: We identified two null-mutations (R501X and 2282del4), seven SNPs previously described in databases and three SNPs that had not been previously described. One of the SNP identified in this study (1741A > T) was more frequently detected in patients with non-allergic asthma, worse FVC, FEV1 and PEF values and a higher treatment step. In addition, lowered spirometric values were observed in the non-allergic group carrying any of the nonsynonymous SNPs. Conclusions: In the association study of genetic variants of the FLG gene in our population the 1741A > T polymorphism seems to be associated with non-allergic asthma

Tryptase: genetic and functional considerations.

[EN] Tryptase is one of the main proteases located in the secretory granules of the mast cells, and is released through degranulation. It is therefore assumed to play an important role in inflammatory and allergic processes. Four genes are known to encode for these enzymes, with different alleles that give rise to different types of tryptases. The term "tryptase" generally refers to β-tryptase, which in vivo is a heterotetramer, possessing a structure of vital importance for enabling drug and substrate access to the active site of the molecule. Tryptase has been reported to possess antagonistic functions, since it plays an important role both in inflammatory phenomena and as a protector against infection. In allergic processes it is associated to bronchial hyperresponsiveness in asthmatic patients, where PAR-2 is of great importance as an airway receptor. Lastly, the genes that encode for tryptase are highly polymorphic and complex. As a result, it is important to establish a relationship between genotype and phenotype in disorders such as asthma, and to identify mutations that are presumably of pharmacological relevance

A new PTGDR promoter polymorphism in a population of children with asthma.

[EN] Recently, functional genetic variants of the PTGDR gene have been associated with asthma. The objective of this work was to study polymorphisms of the promoter region of PTGDR and their haplotype and diplotype combinations in a Spanish population of children with asthma. In this study, 200 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the ATS criteria. The polymorphisms were analyzed by direct sequencing. In the study, the new polymorphism (-613C > T) in the promoter region of PTGDR was analyzed. The CT genotype was more common in controls (17%) than in patients with asthma (1%) (p-value = 0.0003; OR, 0.057; 95% CI, 0.007-0.441). The CCCT CCCC diplotype (promoter positions -613, -549, -441, and -197) was more frequent in the group of patients with asthma [Fisher's p-value = 0.012; OR, 10.24; 95% CI (1.25-83.68)]; this diplotype is unambiguous. To our knowledge, this is the first study of -613C > T PTGDR polymorphism in patients. This analysis provides more complete information on influence of diplotype combinations of PTGDR polymorphisms in asthma.Fundación para la Investigación de la Sociedad Española de Alergología e Inmunología Clínica

Genome-wide association studies (GWAS) and their importance in asthma

[EN] Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease.FEDER funds; Junta de Castilla y León; Fundación Botín-Universidad de Salamanca; Sociedad Española de Alergología e Inmunología Clínica; Fundación Salud 200

Acute Impacts of Different Types of Exercise on Circulating α-Klotho Protein Levels

[EN] Elevated plasma α-klotho (αKl) protects against several ageing phenotypes and has been proposed as a biomarker of a good prognosis for different diseases. The beneficial health effects of elevated plasma levels of soluble αKl (SαKl) have been likened to the positive effects of exercise on ageing and chronic disease progression. It has also been established that molecular responses and adaptations differ according to exercise dose. The aim of this study is to compare the acute SαKl response to different exercise interventions, cardiorespiratory, and strength exercise in healthy, physically active men and to examine the behavior of SαKl 72h after acute strength exercise.S

Genome-wide expression profiling of B lymphocytes reveals IL4R increase in allergic asthma

[EN] Allergic asthma is a multifactorial disorder in which activation and differentiation of B lymphocytes toward the production of IgE play an essential role. In these B cells, molecular mechanisms to generate IgE antibodies from IgM depend on a complex network of molecules that trigger class-switch recombination specifically at the Sε region of the IgH locus. Several trans-membrane receptors and activating signaling cascades are known to physiologically participate in these processes, including the IL4R signaling pathway. In this regard, our group has studied in the past genetic polymorphisms in the IL4/IL4R pathway that might hold clinical correlations with atopy and asthma.Spanish Ministry of Health (FIS - Fondo de Investigación Sanitaria); Instituto de Salud Carlos III; FEDER - Fondo Europeo de Desarrollo Regional funds; Spanish Society of Allergology and Clinical Immunolog