Background Prospective genetic evaluation of patients at our referral research hospital presents clinical research challenges. Objective This study sought not only a single-gene explanation for participants’ immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune-phenotype and other heritable comorbidities relevant

Rationale Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen following parasitic worm infections. The use of human monoclonal antibodies (mAbs) allow for an unbiased, comprehensive characterization of the immunodominant antigens targeted by IgE in conditions (e.g., allergy, helminth infection) associated with

Background Germline mutations of signal transducer and activator of transcription 3 (STAT3) are responsible for two distinct human diseases: autosomal-dominant hyper-immunoglobulin E syndrome (AD-HIES) caused by STAT3 loss-of-function (STAT3-LOF) mutations and STAT3 gain-of-function (STAT3-GOF) disease. So far, these entities have been regarded as antithetic, with AD-HIES mainly associated with characteristic

Background Worldwide, pollen of the weed mugwort (Artemisia vulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and the corresponding HLA have been made. Objective We sought to characterize IgE epitopes

Background During the first year of life, B cell level is a valuable indicator of whether external factors, such as exposure to B cell depleting therapies, have an adverse impact on immune system development. However, there are no standard reference ranges of B cell levels in healthy infants by age. Objective To estimate the normal range of B cell levels in infants, by age, during the first year of

Background Aspirin-exacerbated respiratory disease (AERD) patients regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary

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Asthma is a common complex respiratory disease characterized by chronic airway inflammation and partially reversible airflow obstruction resulting from genetic and environmental determinants. Because epigenetic marks influence gene expression and can be modified by both environmental exposures and genetic variation, they are increasingly recognized as relevant to the pathogenesis of asthma and may

Background Oral immunotherapy (OIT) leads to suppression of mast cell and basophil degranulation along with changes in the adaptive immune response. Objective We aimed to determine how rapidly these effects occur during OIT and more broadly, the kinetics of basophil and mast cell suppression throughout the course of therapy. Methods Twenty participants, aged 4-12, were enrolled in a peanut OIT trial

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Background Genetic predisposition increases risk for asthma, and distinct nasal microbial compositions are associated with asthma. Host genetics might shape nasal microbiome composition. Objective We examined associations between host genetics and nasal microbiome composition. Methods Nasal samples were collected from 584 participants from the Mount Sinai Health System, New York, USA. Seventy-seven

Establishing tolerance remains a central, if elusive, goal of transplantation. In solid-organ transplantation, one strategy for inducing tolerance has been cotransplantation of various forms of thymic tissue along with another organ. As one of the biological foundations of central tolerance, thymic tissue carries with it the ability to induce tolerance to any other organ or tissue from the same donor

Background Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. Objective To identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. Methods We performed univariate and bivariate genome-wide association analyses

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Background Whether children and people with asthma and allergic diseases are at increased risk for SARS-CoV-2 infection is unknown. Objective To determine SARS-CoV-2 infection incidence in households with children, and whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. Methods Biweekly nasal swabs and weekly surveys were conducted for

Background Cystatin SN/SA (CST1/2) are cysteine protease inhibitors which protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP), however, their role in promoting type 2 inflammation remains poorly characterized. Objective The purpose of this study was to use integrated poly-omics

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Chronic spontaneous urticaria (CSU) is a debilitating mast cell–driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune

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Background Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma. Objective To endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. Methods Multi-omics analysis using

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Background Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity, however the mechanisms driving this have not been widely studied. Objective To characterize the phenotypic and transcriptomic features of experimental

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In the years since the SARS-CoV-2 pandemic began and spread across the globe, lessons have been learned about the challenges and opportunities a pandemic brings to humankind. Researchers have produced many vaccines at unprecedented speed to protect people but have also been cognizant of the challenges presented by a new and unexpected infectious disease. The scope of this review is to examine the path

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Background & Aims Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring

Background Asthma disproportionately affects African-American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood. Objective To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate-severe asthma

Background Asthma is the most common chronic condition in children and the third leading cause of hospitalization in pediatrics. The genome-wide association study catalog reports 140 studies with genome wide significance. A polygenic risk score (PRS) with predictive value across ancestries has not been evaluated for this important trait. Objective We aim to train and validate a PRS relying on genetic

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Recent events involving the global coronavirus pandemic have focused attention on vaccination strategies. While tremendous advances have been made in subcutaneous and intramuscular vaccines during this time, one area that has lagged in implementation is mucosal immunization. Mucosal immunization provides several potential advantages over subcutaneous and intramuscular routes, including protection from

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Background How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs (SLOs and TLOs) in patients with elevated tissue expression levels of IgE (Kimura’s disease, KD) and

Background The mitochondrial fission protein, dynamin related protein 1 (Drp1), has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro but its functions in MCs activated by various stimuli in vivo has not been examined. Objective Analyze Drp1 function in both mouse and human MCs. Methods We used human peripheral blood-derived cultured MCs (PBCMCs) and two genetic mouse

Background The oral and gut microbiomes have each been associated with food allergy status. Within food allergy, they may also influence reaction thresholds. Objective To identify oral and gut microbiota associated with reaction thresholds in peanut allergy. Methods 59 children ages 4 to 14 years with suspected peanut allergy underwent double-blind, placebo-controlled food challenge to peanut. Children

Background Patients with systemic mastocytosis often have symptoms of mast cell activation which is associated with elevated levels of urinary mast cell mediator metabolites. Patients with hereditary alpha-tryptasemia (HαT) may present with symptoms of mast cell activation. It is not known whether levels of mast cell mediators are elevated in this patient population. Objective The purpose of this study

Background Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis. Objective This post hoc exploratory analysis of the phase II tralokinumab trial, MESOS (NCT02449473), aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma. Methods The T2 and T17 gene expression signatures, 3- and 5- gene mean (3- and 5GM)

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