Background Patients with mast cell activation symptoms and elevated baseline serum tryptase (MCAS-T) may not necessarily have a clonal mast cell disorder. Many are diagnosed with hereditary alpha tryptasemia (HαT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding alpha-tryptase and increased risk for severe anaphylaxis. Objective The aim of our study

Background T helper (Th) 2 cells were thought to be a pivotal factor for initiation of the autoimmune blistering disease pemphigus. However, the role of other T cell subsets in pemphigus pathogenesis remained unclear. Objective We aimed to characterize the exact phenotype of T cells responsible for the development of pemphigus. Methods Whole transcriptome shotgun sequencing was performed to determine

Background Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. Objective We hypothesized that 129Xe MRI is feasible and can demonstrate

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, typically characterized by a type 2 inflammatory reaction and by comorbidities including asthma, N-ERD and allergies. EUFOREA, the European Forum for Research and Education in Allergy and Airway Diseases, here proposes structured definitions to enable communication between

Background Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19. Objective To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods Secondary analysis of prospective observational cohort studies

Background Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, thus taking away the option of therapeutic management focused on eliminating the inciting agent. Epinephrine and antihistamines followed by systemic corticosteroids are the mainstays of therapy for acute events. There is no prophylactic therapy that reliably prevents anaphylaxis. Objective We sought to determine the efficacy of omalizumab

Allergies to peanuts, tree nuts, and sesame seeds are among the most important food related causes of anaphylaxis. Important clinical questions include: why is there a variable occurrence of co-allergy among these foods and is this immunologically mediated? Clinical and immunological data summarized here suggest an immunologic basis for these co-allergies based on similarities among the 2S-albumins

Background Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Though frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. Objective To identify differences in the upper airway inflammatory signature between

Background The selective reduction of memory Th2 responses could be key to affording tolerance and protection from the reoccurrence of damaging allergic pathology. Objective We asked whether TNF family costimulatory molecules co-operated to promote accumulation and reactivity of effector memory CD4 T cells to inhaled complex allergen, and if their neutralization could promote airway tolerance to subsequent

Introduction Whether biologic therapies enhance the risk of COVID-19 or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. Objective investigating the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. Materials and methods This is a retrospective

Autoinflammatory diseases are conditions in which pathogenic inflammation arises primarily through antigen-independent hyperactivation of immune pathways. First recognized just over 2 decades ago, the autoinflammatory disease spectrum has expanded rapidly to include more than 40 distinct monogenic conditions. Related mechanisms contribute to common conditions such as gout and cardiovascular disease

The major challenge of allergy diagnosis lies in the development of accessible and reliable diagnostics allowing correct prediction of the clinical outcome upon exposure to the offending allergen(s) and cross-reactive structures. Since the late nineties, evidence has accumulated that flow-assisted analysis and quantification of ex vivo activated basophils (BAT) might meet this requirement for different

Autoimmune and inflammatory diseases are common, diverse, and they can affect nearly any organ system. Much of the pathogenesis of these diseases relates to dysregulated cytokine secretion. Historically, autoimmune and inflammatory diseases have been treated with medications that non-specifically suppress the immune system. Monoclonal antibodies that block the action of pathogenic cytokines emerged

Background Proton pump inhibitors (PPIs) have been recognized as a primary treatment of eosinophilic esophagitis (EoE), an allergic inflammatory disease of the esophageal mucosa. The mechanisms underlying esophageal epithelial responses to PPIs remain poorly understood. Objective We hypothesized that PPIs can counteract interleukin 13 (IL-13)–mediated esophageal epithelial responses that are germane

Background Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Prior genome-wide association studies (GWAS) have provided strong evidence for three genome-wide susceptibility loci. Objective We aimed to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported datasets

Background Eosinophilic esophagitis (EoE) is a chronic, food antigen–mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation. Objective We hypothesized that very early onset EoE (V-EoE) would be enriched for early life and genetic factors and have worse presentation and prognosis than later onset pediatric EoE (L-EoE). Methods We conducted a single-site

Background Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. Objective To determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). Methods APeX-2 was a double-blind, parallel-group study that randomized patients

Background Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. Objectives In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. Methods Children participating in the Childhood Origins

Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect

The Mas-related G protein–coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin

Background Poor clearance of apoptotic cells has been suggested to contribute to severe asthma, but whether uptake of apoptotic cells by lung phagocytes might dampen House Dust Mite (HDM)-induced lung inflammation has not been shown. Objective We investigated if apoptotic cell engulfment in the murine lung impacts the development of allergen-induced asthmatic airway inflammation and which immune modulating

Background β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (Type I) reactions mediated by antigen-specific IgE. Objective To identify genetic predisposing factors for immediate reactions to β-lactam antibiotics. Methods Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins

Background STAT3 or Dock8 loss-of-function mutations cause HIES and the role of abnormal T cell function has been extensively investigated, however the contribution of B cell intrinsic dysfunction to elevated IgE levels is unclear. Objective We sought to determine the underlying molecular mechanism of how STAT3 regulates BCR signaling, B cell differentiation, and IgE production. Methods We used samples

Background The COVID-19 pandemic has led to surges of patients presenting to emergency departments (ED) and potentially overwhelming health systems. Objective This study aimed to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome. Methods Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations

Background Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. While alterations in the skin microbiome have been described in AD subjects during progression to flare state, the prognostic value of baseline microbiome configurations has not been

Background Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunological processes that determine the course of an exacerbation remains poorly understood, impeding the progression of developing effective therapies. Objective To identify candidate genes that are strongly associated with asthma exacerbation

Obesity has been well recognized as an important comorbidity in patients with asthma, representing a unique phenotype and endotype. This association indicates a close relationship between metabolic and inflammatory dysregulation. However, the detailed organ-organ, cellular, and molecular interactions are not completely resolved. Because of that, the relationship between obesity and asthma remains unclear

The nuclear factor kappa B (NF-κB) signaling system, a key regulator of immunologic processes, also affects a plethora of metabolic changes associated with inflammation and the immune response. NF-κB–regulating signaling cascades, in concert with NF-κB–mediated transcriptional events, control the metabolism at several levels. NF-κB modulates apical components of metabolic processes including metabolic

Metabolic inflammation (metaflammation) is characteristic of obesity-related metabolic disorders, associated with increased risk of development of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), or cardiovascular disease. Metaflammation refers to a chronic, low-grade systemic inflammation as opposed to the classical transient and acute inflammatory responses of the innate immune system.

Background There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). Objective We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19

Background In 2017, the Addendum Guidelines for the Prevention of Peanut Allergy were published with recommendations on early introduction of peanut-containing foods based on infants’ clinical history. Objective We sought to conduct a nationwide US survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy. Methods Survey invitations were delivered

Background S. aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in AD patients is unclear. Objective To identify the S. aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD. Methods In vitro human keratinocyte cell culture, ex vivo human skin

Background SARS-CoV-2 is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed Coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract and skin among others. Objective While several risk

Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6

Since the first textbook devoted to Cytokine Storm Syndromes (CSS) was published in 2019, the world has changed dramatically and the term’s visibility has broadened. Herein, we define CSS broadly to include life/organ-threatening systemic inflammation and immunopathology regardless of the context in which it occurs, recognizing that the indistinct borders of such a definition limit its utility. Nevertheless

Autoinflammatory diseases are monogenic and polygenic disorders due to dysregulation of the innate immune system. The inherited conditions have been clustered with primary immunodeficiencies in the latest practice parameters, however, these diseases have unique clinical presentations, genetics and available therapies. Given the presentation of fevers, rashes and mucosal symptoms observed in many of

The newly described severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is responsible for a pandemic (Corona virus-induced disease -19, COVID-19). It is now well established that certain comorbidities define high risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences

Background Genetic faults in several components of the NF-κB pathway cause immunodeficiency. Most defects lead to combined immunodeficiency with a range of severity. Heterozygous mutations in NFKB1 were associated with common variable immunodeficiency, however, homozygous mutations have not been described. Objective We studied the molecular basis of combined immunodeficiency in a patient who presented

Background There is uncertainty about the impact of SARS-CoV-2 infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe COVID-19. This is relevant not only for these patients but also the general population, as studies of IEIs can unveil key requirements for host defense. Objective Describe the presentation, manifestations and outcome of SARS-CoV-2

Background The pathogenesis of COVID-19 is still incompletely understood, but seems to involve immune activation and immune dysregulation. Objective We examined parameters of activation of different leukocyte subsets in COVID-19 infected patients in relation to disease severity. Methods We analyzed plasma levels of myeloperoxidase (MPO, neutrophil activation), soluble (s) CD25 and soluble T cell immunoglobulin

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the Caucasian population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation. Objective We aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions

Background Very-early-onset inflammatory bowel disease (VEOIBD) is a chronic inflammatory disease of the gastrointestinal tract occurring during infancy or early childhood. NLRP3 inflammasome has emerged as a crucial regulator of intestinal homeostasis; however, whether NLRP3 variants may modify VEOIBD risk is unknown. Objective To investigate whether and how a rare NLRP3 variant, found in 3 patients