Journal of Investigational Allergology and Clinical Immunology最新文献

The complexity of anaphylaxis in terms of clinical features and etiology-pathogenesis makes it difficult to establish precise endotypes that correspond to specific phenotypes. Therefore, interest in unravelling the cellular and molecular mechanisms underlying anaphylactic reactions has grown. A large group of anaphylactic reactions are characterized by the classical immunological mechanism of type I hypersensitivity, which leads to IgE-mediated activation of mast cells and basophils. However, in recent decades, other relevant signaling pathways have emerged. These include IgG-associated neutrophil activation, complement activation, cyclooxygenase metabolism, and direct mast cell activation. In drug-induced anaphylaxis, the Mas-related G protein-coupled receptor (MRGPRX2) plays an interesting role by directly triggering mast cell degranulation. In addition, contact, coagulation, and metabolic systems are activated, while homeostasis is altered, as evidenced by the modulation of proteins such as albumin, phospholipids, and apo- and lipoproteins. In all cases, the release of mediators and/or dysregulation of the systems has an impact on the endothelium, which is actively involved in the pathophysiology of the reactions. Furthermore, recent evidence points to extracellular vesicle- and microRNA-mediated communication between cellular compartments in anaphylaxis, and genetic factors, such as hereditary a-tryptasemia, are associated with risk of severe reaction. In summary, the recognition of cellular and molecular signaling mechanisms will enable better patient phenotyping and management in clinical practice.

Background and objectives: α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated. Objective: To investigate the peripheral immune response to tick bites in humans over time.

Methods: In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry.

Results: A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19+ B cells and B-cell subpopulations, as well as a decrease in γδ CD56+ T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56+ T cells were lower in patients than in controls.

Conclusions: Our study provides evidence of significant changes in several immune cell populations in α-Gal-sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.

Background and objectives: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in gastrointestinal PA symptoms is poorly understood. Objective: This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping.

Methods: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens.

Results: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes.

Conclusions: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Background and objectives: The sting challenge test (SCT) is regarded as the most reliable method for assessing the effectiveness of venom immunotherapy (VIT). However, its predictive value in patients undergoing VIT is unclear. This study aims to evaluate the predictive value of the SCT.

Methods: A multicenter retrospective observational study was conducted on patients receiving VIT who underwent SCT. The study gathered data on patient demographics, diagnosis, immunotherapy details, outcomes of the SCT, and subsequent field stings.

Results: A total of 261 patients were included, and 372 SCTs were recorded. Most patients (75.1%) were men. Mastocytosis was confirmed in 7.7%. The final diagnosis was allergy to Apis mellifera (48.7%), Polistes dominula (36.8%), Vespula species (2.7%), and P dominula plus Vespula species (10.7%). SCTs were performed with Apis in 61.6% overall, Polistes in 34.1%, and Vespula in 4.3%. Most of the SCT results were negative (95.7%). A total of 306 field stings were recorded for 146 patients (56.2%); of these, 95.1% were negative. Among these 146 affected patients, 137 had a negative SCT result, and 130 of these also had a subsequent negative field sting, resulting in a negative predictive value (NPV) for the SCT of 94.9%. Of the patients who experienced a field sting, 9 had a positive SCT, and only 3 had a positive field sting, resulting in a positive predictive value of 33.3%.

Conclusions: SCT is safe, and the high NPV emphasizes the usefulness of this test in assessing the effectiveness of VIT.