Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Microbiome and Allergy: New Insights and Perspectives.

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.

Clinical Approach to Mast Cell Activation Syndrome: A Practical Overview.

The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS.

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field.

Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

Identification of sole parvalbumin as a major allergen: study of cross-reactivity between parvalbumins in a Spanish fish-allergic population.

BACKGROUND: Fish allergy is becoming an important health problem in Spain, a country with the third highest level of fish consumption after Japan and Portugal. The most common fish allergens are parvalbumins. In our area, the most widely consumed fish species are lean, such as whiff (Lepidorhombus whiffiagonis) and sole (Solea solea). Adverse reactions to fish are usually related to these species, a fact that is largely unknown to allergists in other countries. OBJECTIVE: The aim of this study was to identify and purify the major allergen implicated in allergic response to sole and evaluate the IgE cross-reactivity of purified parvalbumins from whiff and sole, which are phylogenetically close, and more distant species (i.e. cod and salmon). METHODS: Eighteen Spanish fish-allergic patients with a positive history of type I allergy to fish were recruited from the clinic. Total protein extracts and purified parvalbumins from whiff and sole were tested for their IgE-binding properties by combining two-dimensional Western blotting and mass spectrometry. The extent of cross-reactivity between these parvalbumins along with cod and salmon parvalbumins was investigated by IgE ELISA inhibition assay. RESULTS: An IgE-binding spot of approximately 14 kDa was identified as parvalbumin and confirmed as a major allergen in sole extract, which is recognized by almost 70% of the patients. Whiff parvalbumin was recognized by 83.4% of the patients. High cross-reactivity was determined for all purified parvalbumins by IgE inhibition assay. CONCLUSIONS AND CLINICAL RELEVANCE: Sole and whiff parvalbumin were confirmed as major allergens. The parvalbumins of sole, whiff, cod and salmon were highly cross-reactive, thus suggesting a high amino acid sequence identity between them.

Phosphorylation reduces the allergenicity of cow casein in children with selective allergy to goat and sheep milk.

This study aimed to characterize the role of phosphorylation of caseins in selective allergy to goat milk (GM) and sheep milk (SM) in patients with good tolerance to cow milk (CM). We performed skin prick tests with milk and caseins from CM, GM, and SM and immunoblotting and specific immunoglobulin (Ig) E determinations with milk and casein from cow and GM and SM. Sensitization to milk and caseins from goat and sheep was demonstrated in all 3 patients by skin tests, determination of specific IgE, or both. Immunoblotting confirmed that GM/SM proteins but not CM proteins were involved in the allergic symptoms. IgE reacted with several protein bands from the caseins and milk extracts of both sheep and goat. Phosphorylation was involved in the different allergenicity of CM caseins. We report the implication of phosphorylation in the allergenicity of caseins involved in selective allergy to GM and SM.

Contribution of malolactic fermentation by Oenococcus oeni and Lactobacillus plantarum to the changes in the nonanthocyanin polyphenolic composition of red wine.

The changes in the nonanthocyanin phenolic composition during red wine malolactic fermentation carried out spontaneously and by four different starter cultures of the species Oenococcus oeni and Lactobacillus plantarum were examined to determine whether differences in nonanthocyanin polyphenolic compounds could be attributed to the lactic acid bacteria (LAB) strain that performs this important step of the wine-making process. The polyphenolic compounds were analyzed by high-performance liquid chromatography with photodiode array detection and HPLC with electrospray ionization-mass spectrometry detection. The malolactic cultures selected for this study were indigenous wine LAB strains from the A.O.C. Rioja (Spain). Results showed different malolactic behaviors in relation to wine phenolic compositions for O. oeni and L. plantarum, and also, a diversity was found within each group. The hydroxycinnamic acids and their derivatives, the flavonols and their glycosides, the flavanol monomers and oligomers, and trans-resveratrol and its glucoside were the main compounds modified by the different LAB. The wild LAB population exerted a greater impact in the wine content of some of these phenolic compounds than the inoculated selected monocultures of this study.

Microbiome and Allergy: New Insights and Perspectives

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies areincreasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immuneresponse to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skinmicrobiota and atopic dermatitis, and between gut microbiota and food allergy.The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics arethe techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerablyin recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased.Thus, more and more studies are proposing mechanisms for intervention in the microbiota.In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous,and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases.Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy. (AU)

El papel del microbioma en los mecanismos moleculares de las enfermedades alérgicas se ha vuelto muy relevante en los últimos años.Cada vez más estudios sugieren que una composición alterada de la microbiota, o disbiosis, puede resultar en una alteración local ysistémica de la respuesta inmune a alérgenos específicos. En este sentido, se ha establecido un vínculo entre la microbiota pulmonar y laalergia respiratoria, así como la microbiota cutánea y el desarrollo de dermatitis atópica, y la microbiota intestinal y la alergia alimentaria.La composición de la microbiota humana es dinámica y depende de diversos factores asociados al huésped como la dieta, las enfermedadesy el estilo de vida, entre otros. Para el análisis y comprensión de la microbiota, las ómicas son las técnicas de elección. En las últimasdécadas, las técnicas de análisis de microbiota han tenido un gran avance y han aumentado la necesidad de múltiples enfoques paraexplorar y comprender las enfermedades multifactoriales, incluidas las enfermedades alérgicas. De esta manera, cada vez son más losestudios que proponen mecanismos de intervención sobre la microbiota de pacientes.En esta revisión, presentamos los últimos avances encontrados en la literatura sobre la microbiota humana, centrándose en las microbiotasintestinal, cutánea y respiratoria. Discutimos la relación entre el microbioma y el sistema inmunológico, con especial énfasis en lasenfermedades alérgicas. Finalmente, discutimos las principales tecnologías para el estudio del microbioma y los estudios de intervencióndirigidos a la microbiota propuestos para la prevención de alergias. (AU)

Clinical Approach to Mast Cell ActivationSyndrome: A Practical Overview

The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS (AU)

El diagnóstico de síndrome de activación mastocitaria (SAM) se basa en 3 criterios: 1) signos y síntomas específicos de activación mastocitaria aguda, recurrente y sistémica, 2) aumento de los valores de triptasa en un 20% + 2 ng/ml sobre el valor basal de cada individuo en el periodo comprendido entre 1-4 horas desde el inicio del cuadro agudo, y 3) resolución de los síntomas con tratamiento antimediador. Para realizar el diagnóstico de SAM, es preciso emplear métodos diagnósticos altamente sensibles y específicos capaces de detectar bajas cantidades de mastocitos en la médula ósea. El modelo predictivo de la Red Española de Mastocitosis (REMA score) resulta útil para identificar a los pacientes con mayor probabilidad de padecer una patología mastocitaria clonal y que, por tanto, requieren que se nealice un estudio de médula ósea en el proceso diagnóstico. En este artículo, proponemos un algoritmo diagnóstico para SAM y abordamos el manejo de estos pacientes desde un punto de vista práctico en la consulta alergológica (AU)