Journal of Allergy and Clinical Immunology

BACKGROUND: Predominant antibody deficiency (PAD) is the most common category or inborn errors of immunity and is underpinned by impaired generation of appropriate antibody diversity and quantity. In the clinic, responses are interrogated by assessment of vaccination responses, which is central to many PAD diagnoses. However, the composition of the generated antibody repertoire is concealed from traditional quantitative measures of serological responses. Leveraging modern mass spectrometry-based proteomics (MS-proteomics), it is possible to elaborate the molecular features of specific antibody repertoires, which may address current limitations of diagnostic vaccinology...

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVE: We tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHOD: We conducted a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI Study - Prevention of Allergy via Cutaneous Intervention Study)...

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Cystatin SN, encoded by CST1, belongs to the type 2 (T2) cystatin protein superfamily. In the past decade, several publications have highlighted the association between cystatin SN and inflammatory airway diseases including chronic rhinosinusitis, rhinitis, asthma, chronic obstructive pulmonary disease, and chronic hypersensitivity pneumonitis. It is, therefore, crucial to understand the role of cystatin SN in the wider context of T2 inflammatory diseases. Here, we review the expression of cystatin SN in airway-related diseases with different endotypes...

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VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a novel entity manifesting with a multiplicity of clinical features. Somatic mutations of the UBA1 gene in hematopoietic stem cells constitute the genetic basis of VEXAS. As an X-linked disorder, most cases occur in men, classically developing symptoms during the fifth to sixth decade of life. Considering its multidisciplinary nature involving numerous branches of internal medicine, VEXAS has elicited a wide medical interest and several medical conditions have been associated with this disease...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE: To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls...

BACKGROUND: Frequent asthma exacerbators, defined as those experiencing >1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. OBJECTIVE: To determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. METHODS: We performed RNA-sequencing of upper airway cells from both frequent and non-frequent exacerbators enrolled in the Ohio Pediatric Asthma Repository...

BACKGROUND: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. OBJECTIVE: The aim of the RECONSTRUCT study was to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment...

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BACKGROUND: IL-33 plays a major role in the pathogenesis of allergic diseases such as asthma and atopic dermatitis. Upon its release from lung epithelial cells, IL-33 primarily drives type 2 immune responses, accompanied by eosinophilia and robust production of IL-4, IL-5 and IL-13. However, several studies show that IL-33 can also drive a type 1 immune response. OBJECTIVE: Important questions remain regarding the mechanisms that determine whether IL-33 induces a type 1 or type 2 immune response...

BACKGROUND: T1 inflammation (marked by IFN-γ expression) is now consistently identified in subsets of asthma cohorts, but how it contributes to disease remains unclear. OBJECTIVE: We sought to understand the role of CCL5 in asthmatic T1 inflammation, and how it interacts with both T1 and T2 inflammation. METHODS: CCL5, CXCL9 and CXCL10 mRNA expression from sputum bulk RNAseq, as well as clinical/inflammatory data were obtained from the Severe Asthma Research Program (SARPIII)...

BACKGROUND: Regulatory CD4 T cells (Tregs) in the mice gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Tregs in the human gut is limited. OBJECTIVE: Here, we performed a detailed characterization of Foxp3+ CD4 Tregs in human normal small intestine (SI) as well as from transplanted duodenum and celiac disease lesions...

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BACKGROUND: A major route of sensitization to food allergen is through an impaired skin barrier. IL33 and TSLP have both been implicated in epicutaneous sensitization and food allergy, albeit in different murine models. OBJECTIVE: We assessed the respective contributions of TSLP and IL33 to the development of atopic dermatitis (AD) and subsequent food allergy in TSLP and IL33 receptor (ST2) deficient mice using an AD model that does not require tape stripping. METHOD: TSLPR-/- , ST2-/- and BALB/cJ control mice were exposed to 3 weekly epicutaneous skin patches of either saline, OVA, or a combination of OVA and Aspergillus fumigatus (ASP), followed by repeated intragastric OVA challenges and development of food allergy...