Implicaciones clínicas de la investigación básica : inmunología de la enfermedad celíaca : ¿qué debe saber el clínico?

Producción CientíficaLa enfermedad celíaca es un trastorno inflamatorio crónico del intestino delgado que asocia un componente autoinmune y es inducido por la ingestión de gluten de trigo y proteínas similares en individuos genéticamente susceptibles. El gluten contiene péptidos inmunogénicos capaces de estimular linfocitos T CD4+ específicos de la lámina propia, y péptidos tóxicos de acción directa sobre el epitelio. Muchos de estos péptidos son resistentes a la hidrólisis por enzimas digestivas. Se conoce bien el papel de la inmunidad adaptativa frente al gluten, mediada por linfocitos T CD4+ específicos que reconocen péptidos de gluten modificados por la transglutaminasa tisular (TG2) y presentados junto a moléculas HLA-DQ2/DQ8. Se conocen menos los mecanismos de la inmunidad innata que llevan a la activación de los linfocitos intraepiteliales y a la apoptosis de los enterocitos. Las respuestas de la inmunidad innata y adaptativa frente al gluten existen de forma independiente, pero ambas son necesarias para el desarrollo de la inflamación crónica y la lesión intestinal

Is it true that coeliacs do not digest gliadin?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

Producción CientíficaProlyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

Is it true coeliacs do not digest gliadin ?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

Prolyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptor gene polymorphisms

Producción CientíficaThe study of determinants of asthma is a subject of much interest currently, especially the pharmacogenetic aspects of asthma management. Genetic polymorphisms affecting amino-acids at positions 16 and 27 within β2-adrenoceptor (β2AR) gene have been implicated in the asthma phenotypes and influence on the variability observed in response to use of bronchodilator agents used in the treatment of asthma. Whether these polymorphisms alter the bronchoprotection response to -agonist treatment in Spanish asthmatic population is unknown. The aim of this study was to investigate whether genetic polymorphisms within β2AR gene modulate the clinical outcomes of the individual response to β2-agonist therapy and the development of desensitization in Spanish asthmatic patients.Fondo de Investigación Sanitaria y Ministerio de Sanidad, Consumo y Bienestar Social (FIS00648 and 02/3068)Junta de Castilla y León (VA032/04

Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Producción CientíficaDietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNg and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFa, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFa levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNg levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNg levels, maintained by IL-18 alone

ExoMars Raman Laser Spectrometer (RLS): development of chemometric tools to classify ultramafic igneous rocks on Mars

Producción CientíficaThis work aims to evaluate whether the multi-point analysis the ExoMars Raman Laser Spectrometer (RLS) will perform on powdered samples could serve to classify ultramafc rocks on Mars. To do so, the RLS ExoMars Simulator was used to study terrestrial analogues of Martian peridotites and pyroxenites by applying the operational constraints of the Raman spectrometer onboard the Rosalind Franklin rover. Besides qualitative analysis, RLS-dedicated calibration curves have been built to estimate the relative content of olivine and pyroxenes in the samples. These semi-quantitative results, combined with a rough estimate of the concentration ratio between clino- and ortho-pyroxene mineral phases, were used to classify the terrestrial analogues. XRD data were fnally employed as reference to validate Raman results. As this preliminary work suggests, ultramafc rocks on Mars could be efectively classifed through the chemometric analysis of RLS data sets. After optimization, the proposed chemometric tools could be applied to the study of the volcanic geological areas detected at the ExoMars landing site (Oxia Planum), whose mineralogical composition and geological evolution have not been fully understoodProyecto MINECO Retos de la Sociedad. Ref. ESP2017-87690-C3-1-RProyecto MINECO Retos de la Sociedad. Ref. ESP2017-87690-C3-1-

Raman–Mo¨ssbauer–XRD studies of selected samples from ‘‘Los Azulejos” outcrop: A possible analogue for assessing the alteration processes on Mars

The outcrop of ‘‘Los Azulejos” is visible at the interior of the Can˜adas Caldera in Tenerife Island (Spain). It exhibits a great variety of alteration processes that could be considered as terrestrial analogue for several geological processes on Mars. This outcrop is particularly interesting due to the content of clays, zeolite, iron oxides, and sulfates corresponding to a hydrothermal alteration catalogued as ‘‘Azulejos” type alteration. A detailed analysis by portable and laboratory Raman systems as well as other different techniques such as X-ray diffraction (XRD) and Mo¨ssbauer spectroscopy has been carried out (using twin-instruments from Martian lander missions: Mo¨ssbauer spectrometer MIMOS-II from the NASA-MER mission of 2001 and the XRD diffractometer from the NASA-MSL Curiosity mission of 2012). The mineral identification presents the following mineral species: magnetite, goethite, hematite, anatase, rutile, quartz, gregoryite, sulfate (thenardite and hexahydrite), diopside, feldspar, analcime, kaolinite and muscovite. Moreover, the in-situ Raman and Micro- Raman measurements have been performed in order to compare the capabilities of the portable system specially focused for the next ESA Exo-Mars mission. The mineral detection confirms the sub-aerial alteration on the surface and the hydrothermal processes by the volcanic fluid circulations in the fresh part. Therefore, the secondary more abundant mineralization acts as the color agent of the rocks. Thus, the zeolite–illite group is the responsible for the bluish coloration, as well as the feldspars and carbonates for the whitish and the iron oxide for the redish parts. The XRD system was capable to detect a minor proportion of pyroxene, which is not visible by Raman and Mo¨ssbauer spectroscopy due to the ‘‘Azulejos” alteration of the parent material on the outcrop. On the other hand, Mo¨ ssbauer spectroscopy was capable of detecting different types of iron-oxides (Fe3+/2+-oxide phases). These analyses emphasize the strength of the different techniques and the working synergy of the three different techniques together for planetary space missions

Raman semi-quantification on Mars: ExoMars RLS system as a tool to better comprehend the geological evolution of martian crust

Producción CientíficaThis work presents the latest chemometric tools developed by the RLS science team to optimize the scientific outcome of the Raman system onboard the ExoMars 2022 rover. Feldspar, pyroxene and olivine samples were first analyzed through the RLS ExoMars Simulator to determine the spectroscopic indicators to be used for a proper discrimination of mineral phases on Mars. Being the main components of Martian basaltic rocks, lepidocrocite, augite and forsterite were then used as mineral proxies to prepare binary mixtures. By emulating the operational constraints of the RLS, Raman datasets gathered from laboratory mixtures were used to build external calibration curves. Providing excellent coefficients of determination (R2 0.9942÷0.9997), binary curves were finally used to semi-quantify ternary mixtures of feldspar, pyroxene and olivine minerals. As Raman results are in good agreement with real concentration values, this work suggests the RLS could be effectively used to perform semi-quantitative mineralogical studies of the basaltic geological units found at Oxia Planum. As such, crucial information about the geological evolution of Martian Crust could be extrapolated. In light of the outstanding scientific impact this analytical method could have for the ExoMars mission, further methodological improvements to be discussed in a dedicated work are finally proposed.Consejo Europeo de Investigación (grant 687302)Ministerio de Economía, Industria y Competitividad (grants PID2019-107442RB-C31 and RDE2018-102600-T

Semi‐quantification of binary saline solutions by Raman spectroscopy: Implications for Europa

Producción CientíficaThe Europa lander is a concept for a potential future planetary exploration mission which purpose is to characterize the icy shell of Europa and to search for organics. To achieve this objective, the current concept of the lander includes a Raman spectrometer, such as RLS instrument, that could be able to analyze (sub) surface targets in their solid and liquid form. Knowing that ice and brines of Europa are potentially enriched by sulfate and chlorides, this work seeks to evaluate if Raman spectroscopy could be used to semi quantify the saline content of water solutions using space-like instrumentation. To do so, MgSO4 and MgCl2 were used to prepare three sets of water solutions. Raman analyses were then performed by the laboratory simulator of the ExoMars Raman Laser Spectrometer (RLS), which has been defined as the threshold system for the Europa Lander. After data analysis, two different semi-quantification approaches were tested, and their results compared. Although univariate calibration curves proved to successfully quantify the content of SO42− and Cl− anions dissolved in mono-analyte water solutions, this strategy provided very poor results when applied to binary saline mixtures. Overcoming this issue, the non-linearity prediction ability of Artificial Neural Networks (ANNs) in combination with bandfitting allows to successfully resolve the complexity of the vibrational perturbation suffered by the OH region, which is caused by the cross interaction of H2O molecules with different anions.Ministerio de Economía y Competitividad, Grant/Award Number: PID2019-107442RBC31

Machine learning methods applied to combined Raman and LIBS spectra: Implications for mineral discrimination in planetary missions

Producción CientíficaThe combined analysis of geological targets by complementary spectroscopic techniques could enhance the characterization of the mineral phases found on Mars. This is indeed the case with the SuperCam instrument onboard the Perseverance rover. In this framework, the present study seeks to evaluate and compare multiple machine learning techniques for the characterization of carbonate minerals based on Raman-LIBS (Laser-Induced Breakdown Spectroscopy) spectroscopic data. To do so, a Ca-Mg prediction curve was created by mixing hydromagnesite and calcite at different concentration ratios. After their characterization by Raman and LIBS spectroscopy, different multivariable machine learning (Gaussian process regression, support vector machines, ensembles of trees, and artificial neural networks) were used to predict the concentration ratio of each sample from their respective datasets. The results obtained by separately analyzing Raman and LIBS data were then compared to those obtained by combining them. By comparing their performance, this work demonstrates that mineral discrimination based on Gaussian and ensemble methods optimized the combine of Raman-LIBS dataset outperformed those ensured by Raman and LIBS data alone. This demonstrated that the fusion of data combination and machine learning is a promising approach to optimize the analysis of spectroscopic data returned from Mars.Agencia Estatal de Investigación, grant (PID2022-142490OB-C32)Ministerio de Economía y Competitividad (MINECO),Grant/Award Number (RDE2018-102600-T