El síndrome oral alérgico en la polinosis

págs.: 43-49Capítulo incluido en el libro: Abordaje integral del paciente con asma por alergia al polen del olivo. Manuel Alcántara Villar (coordinador). Sevilla: Universidad Internacional de Andalucía, 2014. ISBN 978-84-7993-255-8. Enlace: http://hdl.handle.net/10334/362

Alergia al polen de olivo : alérgenos y formas clínicas de la polinosis

págs.: 13-26Capítulo incluido en el libro: Abordaje integral del paciente con asma por alergia al polen del olivo. Manuel Alcántara Villar (coordinador). Sevilla: Universidad Internacional de Andalucía, 2014. ISBN 978-84-7993-255-8. Enlace: http://hdl.handle.net/10334/362

La enfermedad respiratoria exacerbada por AINE

págs.: 289-303Capítulo incluido en el libro: Asma y alergia: la epidemia del siglo XXI. Manuel Alcántara Villar (Coordinador). Sevilla: Universidad Internacional de Andalucía, 2012. ISBN 978-84-7993-227-5. Enlace: http://hdl.handle.net/10334/359

La rinitis polínica : manejo clínico y asociación con asma bronquial

págs.: 29-39Capítulo incluido en el libro: Abordaje integral del paciente con asma por alergia al polen del olivo. Manuel Alcántara Villar (coordinador). Sevilla: Universidad Internacional de Andalucía, 2014. ISBN 978-84-7993-255-8. Enlace: http://hdl.handle.net/10334/362

Nonallergic asthma and its severity: Biomarkers for its discrimination in peripheral samples

Asthma is a complex and heterogeneous respiratory disorder characterized by chronic airway inflammation. It has generally been associated with allergic mechanisms related to type 2 airway inflammation. Nevertheless, between 10 and 33% of asthmatic individuals have nonallergic asthma (NA). Several targeted treatments are in clinical development for patients with Th2 immune response, but few biomarkers are been defined for low or non-Th2-mediated inflammation asthma. We have recently defined by gene expression a set of genes as potential biomarkers of NA, mainly associated with disease severity: IL10, MSR1, PHLDA1, SERPINB2, CHI3L1, IL8, and PI3. Here, we analyzed their protein expression and specificity using sera and isolated peripheral blood mononuclear cells (PBMCs). First, protein quantification was carried out using ELISA (in sera) or Western blot (proteins extracted from PBMCs by Trizol procedure), depending on the biomarker in 30 healthy controls (C) subjects and 30 NA patients. A receiver operating characteristic curve analysis was performed by using the R program to study the specificity and sensitivity of the candidate biomarkers at a gene- and protein expression level. Four kinds of comparisons were performed: total NA group vs C group, severe NA patients vs C, moderate-mild NA patients vs C, and severe NA patients vs moderate-mild NA patients. We found that all the single genes showed good sensitivity vs specificity for some phenotypic discrimination, with CHI3L1 and PI3 exhibiting the best results for C vs NA: CHI3L1 area under the curve (AUC) (CI 95%): 0.95 (0.84-1.00) and PI3 AUC: 0.99 (0.98-1.00); C vs severe NA: PI3 AUC: 1 (0.99-1.00); and C vs moderate-mild NA: CHI3L1 AUC: 1 (0.99-1.00) and PI3 AUC: 0.99 (0.96-1.00). However, the results for discriminating asthma disease and severity with protein expression were better when two or three biomarkers were combined. In conclusion, individual genes and combinations of proteins have been evaluated as reliable biomarkers for classifying NA subjects and their severity. These new panels could be good diagnostic tests.This work was supported in part by research grants supported in part by research grants PI13/01730 and PI17/01682, cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). SB was supported by Fundación Conchita Rábago. DC was supported by a contract from Comunidad de Madrid (PEJD-2016/BMD-2682, Sistema de Garantía Juvenil), and LC-J was supported by a contract from MINECO (PEJ-2014-A-31609, Sistema de Garantía Juvenil), both cofinanced by Fondo Social Europeo (FSE) and Iniciativa de Empleo Juvenil (IEJ)

Discriminatory molecular biomarkers of allergic and nonallergic asthma and its severity

The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Asthma is a complex disease comprising various phenotypes and endotypes, all of which still need solid biomarkers for accurate classification. In a previous study, we defined specific genes related to asthma and respiratory allergy by studying the expression of 94 genes in a population composed of 4 groups of subjects: healthy control, nonallergic asthmatic, asthmatic allergic, and nonasthmatic allergic patients. An analysis of differential gene expression between controls and patients revealed a set of statistically relevant genes mainly associated with disease severity, i.e., CHI3L1, IL-8, IL-10, MSR1, PHLDA1, PI3, and SERPINB2. Here, we analyzed whether these genes and their proteins could be potential asthma biomarkers to distinguish between nonallergic asthmatic and asthmatic allergic subjects. Protein quantification was determined by ELISA (in serum) or Western blot (in protein extracted from peripheral blood mononuclear cells or PBMCs). Statistical analyses were performed by unpaired t-test using the Graph-Pad program. The sensitivity and specificity of the gene and protein expression of several candidate biomarkers in differentiating the two groups (and the severity subgroups) was performed by receiver operating characteristic (ROC) curve analysis using the R program. The ROC curve analysis determined single genes with good sensitivity and specificity for discriminating some of the phenotypes. However, interesting combinations of two or three protein biomarkers were found to distinguish the asthma disease and disease severity between the different phenotypes of this pathology using reproducible techniques in easy-to-obtain samples. Gene and protein panels formed by single biomarkers and biomarker combinations have been defined in easily obtainable samples and by standardized techniques. These panels could be useful for characterizing phenotypes of asthma, specifically when differentiating asthma severity.Supported in part by research grants PI13/01730 and PI17/01682, cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). SB was supported by a grant from the Fundación Conchita Rábago and PI17/01682. DC was supported by a contract from Madrid regional government (PEJD-2016/BMD-2682, Sistema de Garantía Juvenil), LC-J was supported by a contract from MINECO (PEJ-2014-A- 31609, Sistema de Garantía Juvenil), and MdP was supported by a contract from Madrid regional government (PEJ-2017- AI/SAL-5938, Sistema de Garantía Juvenil), all cofinanced by The European Social Fund (ESF) and the Youth Employment Initiative (YEI

Anafilaxia. Manejo práctico de autoinyectores de adrenalina

17 páginas.Capítulo incluido en el libro: Actualización en alergología para médicos de atención primaria. Manuel Alcántara Villar (Coordinador). Sevilla: Universidad Internacional de Andalucía, 2018. ISBN 978-84-7993-340-1. Enlace: http://hdl.handle.net/10334/3910

Therapeutic potential of peptides from Ole e 1 in olive-pollen allergy

Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approachesSupported by research grants PI13/01730, PI17/01682 cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). D. Calzada was supported by a contract from Comunidad de Madrid (PEJD-2016/BMD- 2682, Sistema de Garantía Juvenil), L. Cremades-Jimeno was supported by a contract from MINECO (PEJ-2014-A-31609, Sistema de Garantía Juvenil) and MA. de Pedro was supported by a contract from Comunidad de Madrid (PEJ-2017-AI/SAL-5938, Sistema de Garantía Juvenil), all cofinanced by Fondo Social Europeo (FSE) and Iniciativa de Empleo Juvenil (IEJ). S. Baos was supported by Fundación Conchita Rábago and PI17/01682

An Enzymatically Active β-1,3-Glucanase from Ash Pollen with Allergenic Properties: A Particular Member in the Oleaceae Family

Endo-β-1,3-glucanases are widespread enzymes with glycosyl hydrolitic activity involved in carbohydrate remodelling during the germination and pollen tube growth. Although members of this protein family with allergenic activity have been reported, their effective contribution to allergy is little known. In this work, we identified Fra e 9 as a novel allergenic β-1,3-glucanase from ash pollen. We produced the catalytic and carbohydrate-binding domains as two independent recombinant proteins and characterized them from structural, biochemical and immunological point of view in comparison to their counterparts from olive pollen. We showed that despite having significant differences in biochemical activity Fra e 9 and Ole e 9 display similar IgE-binding capacity, suggesting that β-1,3-glucanases represent an heterogeneous family that could display intrinsic allergenic capacity. Specific cDNA encoding Fra e 9 was cloned and sequenced. The full-length cDNA encoded a polypeptide chain of 461 amino acids containing a signal peptide of 29 residues, leading to a mature protein of 47760.2 Da and a pI of 8.66. An N-terminal catalytic domain and a C-terminal carbohydrate-binding module are the components of this enzyme. Despite the phylogenetic proximity to the olive pollen β-1,3-glucanase, Ole e 9, there is only a 39% identity between both sequences. The N- and C-terminal domains have been produced as independent recombinant proteins in Escherichia coli and Pichia pastoris, respectively. Although a low or null enzymatic activity has been associated to long β-1,3-glucanases, the recombinant N-terminal domain has 200-fold higher hydrolytic activity on laminarin than reported for Ole e 9. The C-terminal domain of Fra e 9, a cysteine-rich compact structure, is able to bind laminarin. Both molecules retain comparable IgE-binding capacity when assayed with allergic sera. In summary, the structural and functional comparison between these two closely phylogenetic related enzymes provides novel insights into the complexity of β-1,3-glucanases, representing a heterogeneous protein family with intrinsic allergenic capacity

Nonallergic Asthma and Its Severity: Biomarkers for Its Discrimination in Peripheral Samples

Asthma is a complex and heterogeneous respiratory disorder characterized by chronic airway inflammation. It has generally been associated with allergic mechanisms related to type 2 airway inflammation. Nevertheless, between 10 and 33% of asthmatic individuals have nonallergic asthma (NA). Several targeted treatments are in clinical development for patients with Th2 immune response, but few biomarkers are been defined for low or non-Th2-mediated inflammation asthma. We have recently defined by gene expression a set of genes as potential biomarkers of NA, mainly associated with disease severity: IL10, MSR1, PHLDA1, SERPINB2, CHI3L1, IL8, and PI3. Here, we analyzed their protein expression and specificity using sera and isolated peripheral blood mononuclear cells (PBMCs). First, protein quantification was carried out using ELISA (in sera) or Western blot (proteins extracted from PBMCs by Trizol procedure), depending on the biomarker in 30 healthy controls (C) subjects and 30 NA patients. A receiver operating characteristic curve analysis was performed by using the R program to study the specificity and sensitivity of the candidate biomarkers at a gene- and protein expression level. Four kinds of comparisons were performed: total NA group vs C group, severe NA patients vs C, moderate–mild NA patients vs C, and severe NA patients vs moderate–mild NA patients. We found that all the single genes showed good sensitivity vs specificity for some phenotypic discrimination, with CHI3L1 and PI3 exhibiting the best results for C vs NA: CHI3L1 area under the curve (AUC) (CI 95%): 0.95 (0.84–1.00) and PI3 AUC: 0.99 (0.98–1.00); C vs severe NA: PI3 AUC: 1 (0.99–1.00); and C vs moderate–mild NA: CHI3L1 AUC: 1 (0.99–1.00) and PI3 AUC: 0.99 (0.96–1.00). However, the results for discriminating asthma disease and severity with protein expression were better when two or three biomarkers were combined. In conclusion, individual genes and combinations of proteins have been evaluated as reliable biomarkers for classifying NA subjects and their severity. These new panels could be good diagnostic tests