Journal of Allergy and Clinical Immunology

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BACKGROUND: Immunoglobulin E, IgE)-mediated degranulation of mast cells, MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association. OBJECTIVE: We sought to elucidate the molecular basis of the MC-blood vessel interaction and to determine its relevance for IgE-mediated immune responses...

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the US. Through the depletion of circulating IgE and the subsequent reduction of FCεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation...

BACKGROUND: Neutrophilic asthma (NA) is a severe asthma phenotype associated with steroid resistance and IL-1β overproduction; however, the exact mechanism remains unclear. Moreover, the dysfunction of tumor necrosis factor-alpha signaling pathway, a regulator of IL-1β production, was associated with the deficiency of OTU deubiquitinase with linear linkage specificity (otulin) in autoimmune patients. OBJECTIVE: We hypothesized that otulin downregulation in macrophages (Mφ) could trigger Mφ activation via the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway...

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of CU patients has not been reported. OBJECTIVE: To explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 CU patients and 82 healthy controls (HCs) were collected for metabolomics quantification and performed bioinformatics analysis...

BACKGROUND: Siglec-3 (CD33) is a major Siglec expressed on human mast cells and basophils and engagement of CD33 leads to inhibition of cellular signaling via immunoreceptor tyrosine-based inhibitory motifs (ITIMs). OBJECTIVE: We sought to inhibit human basophil degranulation by simultaneously recruiting inhibitory CD33 to the IgE-FcεRI complex using monoclonal anti-IgE directly conjugated to CD33 ligand (CD33L). METHODS: Direct and indirect basophil activation tests (BAT) were used to assess both antigen-specific (peanut) and antigen non-specific (polyclonal anti-IgE) stimulation...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. METHODS: We studied seven relatives with autoimmune/inflammatory diseases and lymphoproliferative diseases. We analysed biopsy results and performed whole-exome sequencing and immunological studies...

BACKGROUND: Allergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization impacts lung function over time. OBJECTIVE: To test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood. METHODS: We analyzed longitudinal measurements of lung function (spirometry, impulse oscillometry) and allergic sensitization (aeroallergen skin tests, serum allergen-specific IgE) throughout early childhood in the Urban Environmental and Childhood Asthma study which included high-risk urban children living in disadvantaged neighborhoods...

Current treatments of eosinophilic esophagitis (EoE) aim to eliminate esophageal mucosal inflammation and attenuate, stabilize, or reverse stricture formation. However, our ability to study the long-term course of esophageal strictures in patients with EoE is hampered by the short-term existence of this disease. t is unclear to what degree of control of inflammation is needed to prevent stricture formation. Additionally, identified phenotypes of EoE, may ultimately dictate different levels of concern and time intervals for developing fibrosis...

Gene editing technology has emerged as a powerful tool in all aspects of health research and continues to advance our understanding of critical and essential elements in disease pathophysiology. The clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology has been used with precision to generate gene knockouts, alter genes, and to identify genes that cause disease. The full spectrum of allergic/atopic diseases, in part because of shared pathophysiology, is ripe for studies with this technology...

BACKGROUND: Prior studies have reported that renal insufficiency occurs in a small percentage of patients with predominantly antibody deficiency (PAD) and in about 2% of patients with common variable immunodeficiency (CVID). OBJECTIVE: The goal of our study was to understand and evaluate the prevalence and type of renal complications in PAD patients in the United States Immunodeficiency Network (USIDNET) cohort. We hypothesized there is an association between certain renal complications and severity of immunophenotype in patients with PAD...

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BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form...

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation often in response to food allergen exposure. Common among all EGIDs is a clinical presentation characterized by a history of atopic disease with a variety of gastrointestinal symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs...

BACKGROUND: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. OBJECTIVE: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort. METHODS: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811)...

BACKGROUND: A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. OBJECTIVE: We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. METHODS: We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21)...

BACKGROUND: Acute infusion reactions to oxaliplatin, a chemotherapeutic used to treat gastrointestinal cancers, are observed in about 20% of patients. Rapid drug desensitization (RDD) protocols often allow the continuation of oxaliplatin in patients with no alternative options. Break-through symptoms including anaphylaxis can still occur during RDDs. OBJECTIVE: To evaluate if pretreatment with acalabrutinib, a Bruton's tyrosine kinase inhibitor, can prevent anaphylaxis during a RDD in a patient sensitized to oxaliplatin...

No abstract text is available yet for this article.