Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for the assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a subgroup-specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

Allergen Stability in Food Allergy: A Clinician's Perspective.

PURPOSE OF REVIEW: The globally rising food allergy prevalence is associated with the urgent need for new disease prevention methods, efficient treatment, and reliable risk assessment methods for characterization of food allergens. Due to inter-individual variations in the digestive system, food allergens are degraded to a different extent in each person. Food processing also influences allergen digestion. RECENT FINDINGS: In this review, we provide an overview of the digestive system with focus on relevance for food allergy. Main food proteins causing allergic reactions are evaluated, and the combined role of food processing and digestion for allergen stability is highlighted. Finally, clinical implications of this knowledge are discussed. Recent literature shows that allergen digestibility is dependent on food processing, digestive conditions, and food matrix. Digestion affects proteins allergenicity. It is currently not possible to predict the immunogenicity of allergens solely based on protein stability.

Real-life evaluation of molecular multiplex IgE test methods in the diagnosis of pollen associated food allergy.

BACKGROUND: Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)-sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX2 ) in the context of pollen food syndrome (PFS) diagnosis in a real-life scenario, to assess the benefit of multiplex testing in PFS patients. METHODS: Diagnosis of food allergy was performed in 53 patients. Allergen-sIgE concentrations were measured with ISAC and ALEX2 . Results for sIgE were statistically compared with each other, with SPT results and with clinical presentation of the patients. RESULTS: Using ISAC as reference test for sIgE measurements, the average sensitivity of ALEX2 for PR-10 allergens was 83.2% and the average specificity 88.0%. If only low sIgE concentrations were included, the sensitivity was 60.8% and the specificity 91.1%. Apple and hazelnut sensitizations were confirmed in most patients by concordance of sIgE and SPT results. Significant correlations were shown between clinical symptoms and Mal d 1- and Gly m 4-sIgE levels measured by both tests and for Cor a 1-sIgE levels measured by ALEX2 . In eight patients, profilin related symptoms were supported by Hev b 8-sensitization. CONCLUSION: Multiplex testing is beneficial to understand patient-specific individual sensitization profiles and to providing personalized management recommendations. In the future, custom-designed test kits might enable reducing costs of multiplex testing for specific patient groups without compromising the diagnostic value.

Food Allergen Nitration Enhances Safety and Efficacy of Oral Immunotherapy in Food Allergy.

(1) Background: Posttranslational protein modifications have been demonstrated to change protein allergenicity. Previously, it was reported that pretreatment with highly nitrated food proteins induced a tolerogenic immune response in an experimental mouse model and in human immune cells. Here, we investigated a possible therapeutic effect of modified proteins and evaluated the safety of oral exposure to highly nitrated proteins in an experimental food allergy model. (2) Methods: BALB/c mice were orally sensitized towards ovalbumin (OVA) under gastric acid suppression. Thereafter, treatment via intragastric gavage with maximally nitrated OVA (nOVAmax) and OVA as a control was performed six times every 2 weeks. On the last day of experiments, all the treated mice were orally challenged with OVA. Systemic anaphylactic reaction was determined by measuring the core body temperature. Moreover, antibody levels, regulatory T cell numbers, cytokine levels and histology of antrum tissues were analyzed. (3) Results: After oral immunotherapy, OVA-specific IgE titers were decreased while IgG1 titers were significantly elevated in the mice receiving OVA. After oral challenge with OVA, nOVAmax-treated allergic animals showed no drop of the core body temperature, which was observed for OVA-allergic and OVA-treated allergic animals. Significantly fewer eosinophils and mast cells were found in the gastric mucosa of the allergic mice after nOVAmax treatment. (4) Conclusions: Oral immunotherapy with nOVAmax reduced allergic reactions upon allergen exposure and the number of allergen effector cells in the gastric mucosa. Thus, maximally nitrated allergens enabled an efficient and safe treatment for food allergy in our experimental model.

The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging.

The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.

Gastric Enzyme Supplementation Inhibits Food Allergy in a BALB/c Mouse Model.

Impaired gastric digestion due to suppressed gastric acidity enhances the risk for food allergy development. In the current study, we aimed to evaluate the impact of a supported gastric digestion via application of a pharmaceutical gastric enzyme solution (GES) on food allergy development and allergic reactions in a BALB/c mouse model. The ability of the GES to restore hypoacidic conditions was tested in mice treated with gastric acid suppression medication. To evaluate the impact on allergic symptoms, mice were orally sensitized with ovalbumin (OVA) under gastric acid suppression and subjected to oral challenges with or without GES. The immune response was evaluated by measurement of antibody titers, cytokine levels, mucosal allergy effector cell influx and regulatory T-cell counts. Clinical response was objectified by core body temperature measurements after oral OVA challenge. Supplementation of GES transiently restored physiological pH levels in the stomach after pharmaceutical gastric acid suppression. During oral sensitization, supplementation of gastric enzymes significantly reduced systemic IgE, IgG1 and IgG2a levels and allergic symptoms. In food allergic mice, clinical symptoms were reduced by co-administration of the gastric enzyme solution. Support of gastric digestion efficiently prevents food allergy induction and alleviates clinical symptoms in our food allergy model.

The clinical implications of the microbiome in the development of allergy diseases.

Introduction: A substantial number of patients worldwide are affected by allergies. Emerging evidence suggests that the individual microbial composition might contribute to the development of allergies or might even protect from allergic diseases.Areas covered: This review provides a detailed summary regarding available knowledge on the composition of a healthy human microbiome at allergy relevant body sites. It highlights factors influencing the microbiota composition. Furthermore, recent findings on the mutual interaction of the microbiota with the innate and adaptive immune system are reported. In the final part, this knowledge is combined to discuss microbial implications for food allergy, allergic asthma, allergic rhinitis, and skin allergies. Literature for this review was gathered by searching PubMed and Google Scholar databases between October and December 2020.Expert opinion: Due to the highly individual composition, it is currently not possible to define the characteristics of a site-specific microbiome in health and disease. Mainly effects of bacterial communities have been investigated, while fungal or viral influences are not yet well understood. The communication between microbial communities found in different organs impact on allergy development. Thus, a personalized approach is essential to beneficially influence these complex interactions and to modulate the host-specific microbiota in allergies.