Functional role of ST6GALNAC1-mediated sialylation of mucins in preserving intestinal barrier integrity and ameliorating inflammation. Authors : Elisa Sánchez-Martínez1*, Manuel Garrido-Romero1,2,*, F. Javier Moreno21Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain.2Department of Bioactivity and Food Analysis, Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC-UAM), Madrid, Spain.*Equal contributionCorrespondence to:F. Javier Moreno. Department of Bioactivity and Food Analysis, Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC-UAM), Nicolás Cabrera 9, 28049 Madrid, Spain.E-mail:email@example.comAbbreviations:ST6GALNAC1, ST6; mucin-2, MUC2; dextran sulfate sodium, DSS; wild-type, WT; short-chain fatty acids, SCFA.Funding information : MGR is supported by an EFSA project (Grant agreement GP/EFSA/ENCO/2020/02 – 1) granted to FJM. Conclusions, findings and opinions expressed in this document reflect only the view of the authors and not the official position of EFSA.Keywords: epithelial barrier; MUC2; intestinal mucus; gut microbiota disruption; colitis.
Background. Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process is lacking. Methods. We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 to December 2020 at Shamir medical Center. Data was compared to that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period. Results. A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n=53), peanut (n=18), sesame (n=7), egg (n=5) and tree nuts (n=13) were analyzed and compared to 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents respectively, p<0.0001) and during home treatment (22.9% vs. 10.5%, p=0.001 for children, and 14.2%, p=0.06 for adolescents). Most adults (61.5%) were fully desensitized, but rates of full desensitization were significantly lower compared to children (73.4%, p=0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment compared to children (14.3%, p=0.015) and adolescents (14.1%, p=0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable to children and adolescents. Conclusions. OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.
Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI. We herein summarize practical resources to support this guideline’s implementation in clinical practice. For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality, and were pragmatically rated for their evidence-basis and user friendliness. Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace, and wider community. Most resources were in English, web-based and had limited evidence-basis. This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care.
Background: Randomized controlled trials (RCTs) are the gold-standard for benefit-risk assessments during drug approval processes. Real-word data (RWD) and the resulting real-world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. Methods: We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long-term effectiveness outcomes and adherence to AIT. Results: 13 respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non-AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma was hampered for most endpoints in patients treated with most preparations compared to the non-AIT group, receiving only anti-asthmatic medication. The results for “time to onset” of asthma were inconsistent. Adherence to AIT decreased during the recommended 3-years treatment period, however in most studies higher adherence to subcutaneous than to sublingual AIT was shown. Conclusion: The analysis of long-term effectiveness outcomes of the RWE studies based on prescription databases confirms the long-term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes.
The incidence of food allergy (FA) has continued to rise over the last several decades, posing significant burdens on health and quality of life. Significant strides into the advancement of FA diagnosis, prevention, and treatment have been made in recent years. In an effort to lower reliance on resource-intensive food challenges, the field has continued work toward the development of highly sensitive and specific assays capable of high-throughput analysis to assist in the diagnosis FA. In looking toward early infancy as a critical period in the development of allergy or acquisition of tolerance, evidence has increasingly suggested that early intervention via the early introduction of food allergens and maintenance of skin barrier function may decrease the risk of FA. As such, largescale investigations are underway evaluating infant feeding and the impact of emollient and steroid use in infants with dry skin for the prevention of allergy. On the other end of the spectrum, the past few years have been witness to an explosive increase in clinical trials of novel and innovative therapeutic strategies aimed at the treatment of FA in those whom the disease has already manifested. A milestone in the field, 2020 marked the approval of the first drug, oral peanut allergen, for the indication of peanut allergy. With a foundation of promising data supporting the safety and efficacy of single- and multi-allergen oral immunotherapy, current efforts have turned toward the use of probiotics, biologic agents, and modified allergens to optimize and improve upon existing paradigms. Through these advancements, the field hopes to gain footing in the ongoing battle against FA.
Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).
Fast gadolinium-based contrast agent challenge test searching for an alternative contrast mediaTo the Editor,Gadolinium-based contrast agents (GBCA) are used in contrast-enhanced magnetic resonance imaging. Hypersensitivity reactions (HSR) to GBCA are scarce, with an incidence of 0.07% and a recurrence rate of 30%, being urticaria the most common presentation (91%), with 0.52/10000 of severe reactions reported1. Recommendation of an alternative GBCA without checking tolerance is dangerous, due to high cross-reactivity between them2. Moreover, premedication is not enough1, showing an overall rate of breakthrough reactions of 39%3.Allergy studies to achieve a safe recommendation in HSR to GBCA have been performed. Negative predictive value of skin-tests to GBCA has been estimated in 84%1. Therefore, more than 10% of patients could react using an alternative negative skin-tested GBCA, and thus, good tolerance to GBCA should be confirmed through a drug challenge-test (DCT)4. These tests are usually performed at graded administrations, and with observation periods between doses1,5. However, since GBCA is usually given as a bolus during radiologic exams, DCT at slow rates cannot be extrapolated to further administrations. Trying to avoid this limitation, we study the tolerance of an alternative GBCA, by means of a fast DCT, approaching the infusion rates used in clinical practice.In accordance with the safety warnings to avoid linear GBCA, we have only used the macrocyclic drugs gadobutrol (Gb) and gadoteric acid (Ga). After obtaining signed informed consent from the patients, skin pricktests (SPT) with undiluted macrocyclic GBCA commercial solutions were done. When SPT at 20 min yielded negative results, intradermal tests (IDT) with 1:10 dilutions were performed, with subsequent readings at both 20 min and 24 hours.A fast DCT with negative skin-tested GBCA was then performed, following our methodology to study HSR to iodinated contrast media, previously described elsewhere6. Doses were 0.2 mg/kg for Ga and 0.1 mg/kg for Gb. First, one third of the total dose of Ga was administered at a rate of 120 cc/hour and, immediately after, the remaining 2/3 at 80 cc/hour. In case of Gb, infusion rates were half those of Ga, i.e., 1/3 at 60 cc/hour and 2/3 at 40 cc/hour. Total infusion time was 8 minutes for both of them. Well-tolerated GBCA was finally recommended for subsequent examinations, and its tolerance was recorded if it was used later.Study results of sixteen patients that were enrolled are summarized in Table 1. They were 12 women and 4 men, with median age of 45.5 years (range 28-73). Adverse reactions to GBCA were immediate in 13 patients (12 urticaria or exanthema, and 1 anaphylaxis), and delayed exanthema in the remaining 3. Gb was involved in 11 reactions, and unknown GBCA in the other 5. Most of the patients (14/16) had been previously exposed to GBCA.Median delay to perform the allergy study was 10 months (range 2-72 months). All skin-tests were negative, except in one patient who showed an immediate positive SPT to Gb, which had been the GBCA involved in the adverse reaction. In our study, we have estimated a negative predictive value of skintests to GBCA of 89%. DCT were negative in 14 patients (12 with Ga, and 2 with Gb). Finally, 15 out of 16 patients had an alternative GBCA, avoiding the use of premedication. In fact, tolerance has been confirmed in 7 of them in subsequent examinations.Safety of our protocol has been confirmed because our 2 positive DCT showed only mild reactions (delayed exanthema and immediate urticarial, both with Ga), and also by including a patient with previous anaphylaxis to GBCA.Here we present a prospective protocol to identify a safe alternative GBCA, including DCT at high infusion rates. Further studies will be necessary on this item/to check this.
Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a “fixed” bronchial obstruction due to structural changes unresponsive to current therapies, from a “reversible” one as demonstrated by lung function normalization during biological therapies not previously obtained even with high dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent tissue-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert “fixed” remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.