The changes induced by hydrodynamic cavitation treatment in wheat gliadin and celiac-toxic peptides.

Hydrodynamic cavitation (HC) is thought weaken the allergenicity of beer gluten proteins. However, the mechanism of action has not been thoroughly studied. In this study, an HC device was used to treat wheat gliadin and two specific celiac-toxic peptides, P1 and P2. FT-IR, MFS, HPLC, and CD were used to monitor the structural characteristics of gliadin and the two peptides. HC reduced the abundance of the coeliac toxic peptides P1 and P2 in solution and the contents of secondary structure ß-turns and PPII, which are related to reduced allergen immunoreactivity. This meant that both the primary and secondary structures of P1 and P2 were affected by HC, leading to fewer allergic reactions. This study was focused on the impact of HC on the secondary structures of allergens produced from gluten raw materials, and it has positive implications for reducing product allergenicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05973-7.

Intragastric administration of transamidated gliadin interferes with the systemic and intestinal immune responses to wheat gliadin in DQ8 transgenic mice.

We have previously shown the ability of transamidated gluten (spf) to modulate both innate and adaptive intestinal immunity elicited by wheat gliadin in HLA-DQ8 transgenic mice (DQ8 mice), a model of gluten sensitivity. Herein, we evaluated the influence of spf when administered intragastrically on the immune response to native gliadin in DQ8 mice. To address the issue, we analysed three regimens of antigen administration: before immunisation (pre-treatment), during immunisation (co-treatment) and through breast milk during the lactating phase (suckling treatment). Mice were immunised mucosally by intranasal delivery of digested wheat gliadin along with cholera toxin in multiple doses. After sacrifice, isolated spleen and mesenteric lymph node (MLN) cells were challenged in vitro and the cytokine profile of culture supernatants assessed by ELISA and multiparametric assay. We found that only pre-treatment with spf was effective in down-regulating the gliadin-specific IFN-γ response and only in spleen cells. Interestingly, spf pre-treatment also induced systemic IL-6, IL-17A and TNF-α. By contrast, we found that spf pre-treatment upregulated INF-γ in MLN but also significantly decreased IL-2. In conclusion, our data provide evidence that the preventive intragastric administration of transamidated gluten is able to interfere with the classical cytokine profile induced by gliadin via mucosal immunisation in a transgenic model expressing one of the HLA molecules associated with coeliac disease.

The Effect of Photobiomodulation and Akkermansia muciniphila on THP-1 Derived Macrophage Polarization Treated with Gliadin Peptide.

Introduction: Photobiomodulation (PBM) and Akkermansia muciniphila have been shown to be effective in improving inflammatory conditions with positive effects on increasing the population of anti-inflammatory M2 macrophages (MQs). In this study, gliadin-stimulated THP-1 derived MQs were treated with A. muciniphila and PBM to evaluate their effects on promoting the polarization of M2 MQs. Methods: The human monocyte cell line (THP-1) was differentiated to MQs. MQs were stimulated with 200 µg/mL gliadin for 24 hours and then treated with PBM 810 nm alone and in combination with A. muciniphila for the following 24 hours to evaluate their effects on MQs polarization. THP-1 derived MQs were also treated with PBM and A. muciniphila to evaluate their effects on non-stimulated MQs. CD11b, CD80, and CD206 levels were evaluated by using the flow cytometry technique. Moreover, the expression of some M1 and M2-related cytokines was determined. Results: PBM therapy of gliadin-stimulated MQs decreased IL-6 and increased TGF-ß, IL-10 and TNF-α expression compared with gliadin exposed MQs. PBM along with A. muciniphila treatment induced IL-6, TNF-α, and IL-10 expression in MQs in comparison to the untreated group. It also elevated TGF-ß, IL-10 and TNF-α levels in gliadin-triggered MQs in comparison to gliadin-stimulated MQ cells. Conclusion: The result of this study showed the potential of PBMT and A. muciniphila for modulating inflammatory responses and MQs polarization. This may open new perspectives to find possible therapeutic targets for celiac diseases.

Gluten Is Not Gluten.

Wheat gluten is responsible for the unique baking properties of wheat flour, but it also causes wheat-related disorders in predisposed individuals. Different commercially available gluten materials are commonly used for a variety of assays, but a detailed characterization of their composition is missing in many cases. This is why we aimed to provide an in-depth analysis of three commonly used gliadin and gluten materials from two different batches using gel electrophoretic and chromatographic techniques. The gliadin material did not show the typical qualitative and quantitative protein composition and does not appear to be representative of wheat gliadin. The two gluten materials had the expected protein composition, but both showed large batch-to-batch variability regarding total protein content. Since these variations result in different biochemical, immunological, and functional behaviors, it is important to analyze at least the total protein content of each material and each batch.

Assessment of the genetic diversity of the alleles of gliadin-coding loci in common wheat (Triticum aestivum L.) collections in Kazakhstan and Russia.

The study of genetic resources using prolamin polymorphism in wheat cultivars from countries with different climatic conditions makes it possible to identify and trace the preference for the selection of the alleles of gliadine-coding loci characteristic of specific conditions. The aim of the study was to determine the "gliadin profile" of the collection of common wheat (Triticum aestivum L.) from breeding centers in Russia and Kazakhstan by studying the genetic diversity of allelic variants of gliadin-coding loci. Intrapopulation (µ ± Sµ) and genetic (H) diversity, the proportion of rare alleles (h ± Sh), identity criterion (I) and genetic similarity (r) of common wheat from eight breeding centers in Russia and Kazakhstan have been calculated. It has been ascertained that the samples of common wheat bred in Kostanay region (Karabalyk Agricultural Experimental Station, Kazakhstan) and Chelyabinsk region (Chelyabinsk Research Institute of Agriculture, Russia) had the highest intrapopulation diversity of gliadin alleles. The proportion of rare alleles (h) at Gli-B1 and Gli-D1 loci was the highest in the wheat cultivars bred by the Federal Center of Agriculture Research of the South-East Region (Saratov region, Russia), which is explained by a high frequency of occurrence of Gli-B1e (86 %) and Gli-D1a (89.9 %) alleles. Based on identity criterion (I), the studied samples of common wheat from different regions of Kazakhstan and Russia have differences in gliadin-coding loci. The highest value of I = 619.0 was found when comparing wheat samples originated from Kostanay and Saratov regions, and the lowest I = 114.4, for wheat cultivars from Tyumen and Chelyabinsk regions. Some region-specific gliadin alleles in wheat samples have been identified. A combination of Gli-A1f, Gli-B1e and Gli-Da alleles has been identified in the majority of wheat samples from Kazakhstan and Russia. Alleles (Gli-A1f, Gli-A1i, Gli-A1m, Gli-A1o, Gli-B1e, Gli-D1a, Gli-D1f, Gli-A2q, Gli-B2o, and Gli-D2a) turned out to be characteristic and were found with varying frequency in wheat cultivars in eight regions of Russia and Kazakhstan. The highest intravarietal polymorphism (51.1 %) was observed in wheat cultivars bred in Omsk region (Russia) and the lowest (16.6 %), in Pavlodar region (Kazakhstan). On the basis of the allele frequencies, a "gliadin profile" of wheat from various regions and breeding institutions of Russia and Kazakhstan was compiled, which can be used for the selection of parent pairs in the breeding process, the control of cultivars during reproduction, as well as for assessing varietal purity.

In Vitro Protective Effect of Pea-Derived Peptides (PPs) via the Keap1/Nrf2 Signaling Pathway on Alpha-Gliadin-Sensitizing Peptide Induced Cacao-2 Cells.

SCOPE: Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. METHODS AND RESULTS: This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway. CONCLUSION: The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

Differential pattern of neurotoxicity induced by the gliadin peptides p31-43 and p57-68 in in vitro model of epilepsy.

Epilepsy is a central nervous system (CNS) disorder causing repeated seizures due to a transient excessive or synchronous alteration in the electrical activity of the brain. Several neurological disorders have been associated to gluten-related diseases (GRD), including epilepsy. However, the molecular mechanisms that associate GRD and epileptogenesis are still unknown. Our previous data have shown that the gliadin peptide 31-43 (p31-43) enhanced number and duration of seizures induced by kainate in mice and exacerbated CA3-kainate-induced neurotoxicity in organotypic hippocampal slices. Here, we investigated whether another important gliadin peptide p57-68 may exerts effects similar to p31-43 on kainate-induced neurotoxicity. We find that both peptides exacerbate kainate-induced damage in the CA3 region once simultaneously challenged. However, after pre-incubation, p31-43 additionally exacerbates neurotoxicity in the CA1 region, while p57-68 does not. These data suggested differential intracellular mechanisms activated by the peptides. Indeed, analysing intracellular signalling pathways we discover that p31-43 induces significant intracellular changes, including increased phosphorylation of Akt, Erk1/2, and p65, decreased p38 phosphorylation, and deacetylation of nuclear histone-3. Based on these observations, we demonstrate that p31-43 likely activates specific intracellular signaling pathways involved in neuronal excitability, inflammation, and epigenetic regulation, which may contribute to its exacerbation of kainate-induced neurotoxicity. In contrast, p57-68 appears to exert its effects through different mechanisms. Further research is necessary to elucidate the precise mechanisms by which these peptides influence neurotoxicity and understand their implications for neurological disorders.

Wheat gliadin/xanthan gum intermolecular complexes: Interaction mechanism and structural characterization.

In this study, the interactions between wheat gliadin (GL) and xanthan gum (XG) were investigated to design new systems with potential applications as a gluten-free substitute product. Combining spectral with morphological and molecular docking methods allowed the establishment of the complexation mechanism between globular hydrophobic GL and the hydrophilic XG with an extended and partially disordered backbone. GL maintains intact its hydrophobic core even at high GL/XG ratios and organizes into small aggregate-type assemblies. The stable and uniform complexes have a low GL content, based on intermolecular hydrogen bonds and hydrophobic interactions. The GL/XG combining ratio influences the size, structure and interaction mechanism of the microparticles. The preferred sites of interaction and the binding affinities were determined by molecular docking on GL libraries and XG models. This research may provide significant knowledge for the development of low-GL wheat food products using a dietary fiber polysaccharide as a functional compound.

Purified Clinoptilolite-Tuff as an Efficient Sorbent for Food-Derived Peanut Allergens.

The avoidance of allergen intake is crucial for persons affected by peanut allergy; however, the cross-contamination of food is common and leads to unpredictable consequences after the consumption of supposedly "safe" food. The aim of the present study was to eliminate harmful traces of peanut allergens from food using purified clinoptilolite-tuff (PCT)-a specially processed zeolite material. Analyses were performed using a peanut ELISA and a Coomassie blue (Bradford) assay. Mimicking conditions of the human gastrointestinal tract demonstrated a higher efficacy of PCT in the intestine (pH 6.8) than in the stomach (pH 1.5). Adsorption rates were fast (<2 min) and indicated high capacities (23 µg and 40 µg per 1 mg of PCT at pH 1.5 and pH 6.8, respectively). Allergenically relevant peanut protein concentrations were sorbed in artificial fluids (32 µg/mL by 4 mg/mL of PCT at pH 1.5 and 80.8 µg/mL by 0.25 mg/mL of PCT at pH 6.8) when imitating a daily dose of 2 g of PCT in an average stomach volume of 500 mL. Experiments focusing on the bioavailability of peanut protein attached to PCT revealed sustained sorption at pH 1.5 and only minor desorption at pH 6.8. Accompanied by gluten, peanut proteins showed competing binding characteristics with PCT. This study therefore demonstrates the potential of PCT in binding relevant quantities of peanut allergens during the digestion of peanut-contaminated food.

Control of the oil content of fried dough sticks through modulating structure change by reconstituted gluten fractions.

In our study, we explored how gluten's role during dough formation and thermal processing can mitigate the adverse effects of physical factors on product quality. We discovered that a gluten network with a gliadin/glutenin ratio of 5:5 effectively limits oil penetration into the dough's core. This particular ratio is found to reduce the exposure of hydrophobic groups due to the presence of hydrated ß-sheet structures. In contrast, gluten networks with higher gliadin proportions than typical wheat gluten tend to be looser, leading to increased chromophore exposure and facilitating more oil absorption. These observations highlighted the complex link between changes in gluten structure, varying protein compositions, and oil content in fried dough sticks. This research provided a foundation for developing specialized low-fat wheat flour and improving the quality of fried dough products.

Vitamin D and celiac disease.

Celiac disease (CD) is an immune-mediated condition affecting the small intestine. Its reported global prevalence falls within the range of 0.7% to 1.4%. Notably, historically, higher rates, reaching 1% in Western Ireland, have been documented. Recent research has even revealed prevalence rates as elevated as 2% in northern Europe. These findings underscore the urgency for swift and cost-effective diagnosis, especially in individuals identified through screening efforts. At present, the diagnosis of CD relies on a multifaceted approach involving positive serological markers such as IgA anti-tissue transglutaminase (anti-TTG) and anti-endomysial antibodies (anti-EMA). These serological findings are assessed in conjunction with classical histological alterations, as outlined in the Marsh classification. CD is an inflammatory condition triggered by the consumption of gluten, resulting from intricate interactions between genetic, immunological, and environmental factors. CD is linked to malabsorption, leading to nutritional deficiencies. Individuals with CD are required to adhere to a gluten-free diet, which itself can lead to nutrient deficiencies. One such deficiency includes vitamin D, and there is substantial experimental evidence supporting the notion of a bidirectional relationship between CD and vitamin D status. A low level of vitamin D has a detrimental impact on the clinical course of the disease. Here we summarize the key characteristics of CD and explore the prominent roles of vitamin D in individuals with CD.

Soft gliadin nanoparticles at air/water interfaces: The transition from a particle-laden layer to a thick protein film.

HYPOTHESIS: Protein-based soft particles possess a unique interfacial deformation behavior, which is difficult to capture and characterize. This complicates the analysis of their interfacial properties. Here, we aim to establish how the particle deformation affects their interfacial structural and mechanical properties. EXPERIMENTS: Gliadin nanoparticles (GNPs) were selected as a model particle. We studied their adsorption behavior, the time-evolution of their morphology, and rheological behavior at the air/water interface by combining dilatational rheology and microstructure imaging. The rheology results were analyzed using Lissajous plots and quantified using the recently developed general stress decomposition (GSD) method. FINDING: Three distinct stages were revealed in the adsorption and rearrangement process. First, spherical GNPs (∼105 nm) adsorbed to the interface. Then, these gradually deformed along the interface direction to a flattened shape, and formed a firm viscoelastic 2D solid film. Finally, further stretching and merging of GNPs at the interface resulted in rearrangement of their internal structure to form a thick film with lower stiffness than the initial film. These results demonstrate that the structure of GNPs confined at the interface is controlled by their deformability, and the latter can be used to tune the properties of prolamin particle-based multiphase systems.

Unraveling the Properties of Phage Display Fab Libraries and Their Use in the Selection of Gliadin-Specific Probes by Applying High-Throughput Nanopore Sequencing.

Directed evolution is a pivotal strategy for new antibody discovery, which allowed the generation of high-affinity Fabs against gliadin from two antibody libraries in our previous studies. One of the libraries was exclusively derived from celiac patients' mRNA (immune library) while the other was obtained through a protein engineering approach (semi-immune library). Recent advances in high-throughput DNA sequencing techniques are revolutionizing research across genomics, epigenomics, and transcriptomics. In the present work, an Oxford Nanopore in-lab sequencing device was used to comprehensively characterize the composition of the constructed libraries, both at the beginning and throughout the phage-mediated selection processes against gliadin. A customized analysis pipeline was used to select high-quality reads, annotate chain distribution, perform sequence analysis, and conduct statistical comparisons between the different selection rounds. Some immunological attributes of the most representative phage variants after the selection process were also determined. Sequencing results revealed the successful transfer of the celiac immune response features to the immune library and the antibodies derived from it, suggesting the crucial role of these features in guiding the selection of high-affinity recombinant Fabs against gliadin. In summary, high-throughput DNA sequencing has improved our understanding of the selection processes aimed at generating molecular binders against gliadin.

The top 100 most cited articles in the past 30 years of wheat allergy: a bibliometric analysis.

Background: Wheat allergy (WA), characterized by immunological responses to wheat proteins, is a gluten-related disorder that has become increasingly recognized in recent years. Bibliometrics involves the quantitative assessment of publications within a specific academic domain. Objectives: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy. Methods: We searched the Web of Science database on 5th Dec 2023. We used the keywords "wheat allergy or wheat anaphylaxis or wheat hypersensitivity," "gliadin allergy or gliadin anaphylaxis or gliadin hypersensitivity," "wheat-dependent exercise-induced anaphylaxis," and "baker's asthma" for our search. All items published between 1993 and 2023 were included. The top 100 most cited articles were identified and analyzed. Results: Our study conducted an in-depth bibliometric analysis of the 100 most-cited articles in the field of wheat allergy, published between 2002 and 2019. These articles originated from 20 different countries, predominantly Japan and Germany. The majority of these articles were centered on the pathogenesis and treatment of wheat allergy (WA). The Journal of Allergy and Clinical Immunology (JACI) was the most prolific contributor to this list, publishing 14 articles. The article with the highest citation count was published by Biomed Central (BMC) and garnered 748 citations. The peak citation year was 2015, with a total of 774 citations, while the years 1998, 2001, and 2005 saw the highest publication frequency, each with 7 articles. Conclusion: Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of wheat allergy, and help clinicians effectively obtain useful articles that have a significant impact on the field of wheat allergy.

Application of electrospinning to fabricate phycocyanin- and Spirulina extract-loaded gliadin fibers for active food packaging.

This study explored the active food packaging application of phycocyanin- and Spirulina extract-loaded gliadin electrospun fibers (GPhy and GSPE5%). SEM findings confirmed that the morphology of fibers was tubular, showing the GPhy and GSPE5% as the optimum fibers. The loading efficiencies of GPhy and GSPE5% were also around 90%, which proved the well-incorporated compounds within the fibers. Simulation results of α-gliadin dissolved in acetic acid illustrated the denaturation of the protein. FTIR and TGA confirmed that after electrospinning the chemical/structural changes and enhanced thermostabilities occurred, respectively. Antibacterial and antioxidant tests detected higher bactericidal and antioxidative effects of GSPE5% than GPhy. In the application part, it was found that GPhy and GSPE5% were able to decrease PV and TBA values as the indications of walnut kernels' protection from lipid oxidation. This work shows a facile and an efficient way to fabricate active food packaging materials using electrospinning and natural compounds.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy.

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Wheat-Based Glues in Conservation and Cultural Heritage: (Dis)solving the Proteome of Flour and Starch Pastes and Their Adhering Properties.

Plant-based adhesives, such as those made from wheat, have been prominently used for books and paper-based objects and are also used as conservation adhesives. Starch paste originates from starch granules, whereas flour paste encompasses the entire wheat endosperm proteome, offering strong adhesive properties due to gluten proteins. From a conservation perspective, understanding the precise nature of the adhesive is vital as the longevity, resilience, and reaction to environmental changes can differ substantially between starch- and flour-based pastes. We devised a proteomics method to discern the protein content of these pastes. Protocols involved extracting soluble proteins using 0.5 M NaCl and 30 mM Tris-HCl solutions and then targeting insoluble proteins, such as gliadins and glutenins, with a buffer containing 7 M urea, 2 M thiourea, 4% CHAPS, 40 mM Tris, and 75 mM DTT. Flour paste's proteome is diverse (1942 proteins across 759 groups), contrasting with starch paste's predominant starch-associated protein makeup (218 proteins in 58 groups). Transformation into pastes reduces proteomes' complexity. Testing on historical bookbindings confirmed the use of flour-based glue, which is rich in gluten and serpins. High levels of deamidation were detected, particularly for glutamine residues, which can impact the solubility and stability of the glue over time. The mass spectrometry proteomics data have been deposited to the ProteomeXchange, Consortium (http://proteomecentral.proteomexchange.org) via the MassIVE partner repository with the data set identifier MSV000093372 (ftp://MSV000093372@massive.ucsd.edu).

Preparation and Characterization of Fish Oil Pickering Emulsions Stabilized by Resveratrol-Loaded Gliadin/Chitin Nanocrystal Composite Nanoparticles.

Unsaturated fatty acids present in fish oil offer various physiological benefits to the human body. However, their susceptibility to oxidation severely limits their potential applications. The purpose of this study was to develop Pickering emulsions stabilized from a composite of resveratrol-loaded gliadin nanoparticles and oxidized chitin nanocrystals (GR/OC) to protect fish oil from oxidation. The effects of the GR/OC composite on the characterizations of fish oil Pickering emulsions were investigated, including the microstructure, physicochemical properties (stability and rheological behavior), and digestion properties in vitro. The results revealed that an increased concentration of the GR/OC composite significantly reduced the droplet size and improved the ambient stability of the emulsions (in terms of pH, ionic strength, temperature, and storage time). Confocal laser scanning microscopy images depicted that the GR/OC nanoparticles were uniformly dispersed at the interface between water and fish oil (W-O interface). This distribution formed a protective envelope around the droplets. Remarkably, the addition of 2% GR/OC nanoparticles stabilized the Pickering emulsions and showed the most positive effect on the antioxidant capacity compared to that of the control group. These stabilized emulsions maintained lower peroxide values and acid values, which were 1.5 times less than those of the blank control during the 14 day accelerated oxidation experiment. Furthermore, the Pickering emulsions stabilized by GR/OC nanoparticles exhibited the ability to protect fish oil from contamination by gastric juices and facilitate the intestinal absorption of omega-3 polyunsaturated fatty acids. The findings suggest that these GR/OC-stabilized Pickering emulsions offer a promising alternative for delivering fish oils in various industries, including the food industry.

PCSK9 inhibition protects mice from food allergy.

The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema. Furthermore, specific PCSK9 inhibition during the elicitation steps of allergic process was sufficient to ensure anti-allergic effects in mice. Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.

Coincidence of antibodies against Hwp1 and ASCA, two distinct molecular targets of Candida albicans, reinforces the link between this fungal species and coeliac disease.

Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibodies (ASCA), a serological marker of Crohn's disease. ASCA has also been reported in other autoimmune diseases, including coeliac disease (CeD). A strong antibody response against Hwp1, a protein associated with invasive hyphal form of C. albicans which presents peptide sequence homologies with gliadin, has also been described in CeD. This observation supports the hypothesis that C. albicans hyphal transition in C. albicans may trigger CeD onset through a mechanism of molecular/antigenic mimicry. In this study, we assessed whether the anti-C. albicans oligomannose and anti-Hwp1 protein responses may be linked despite their different pathophysiological significance. The measurement of ASCA levels in a cohort of patients involved in our previous Hwp1 study showed a significant correlation between the two biomarkers. This new observation further reinforces the link between C. albicans and CeD.