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

Background Whether long-term air pollution exposure has effects on allergic sensitization is controversial. Objective To investigate associations of air pollution exposure at birth and at the time of later biosampling, with IgE sensitization against common food/inhalant allergens, or specific allergen molecules, in children up to 16 years. Methods Up to 6163 children from four European birth cohorts

Background Activation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction of antibody-mediated diseases and ischemia-reperfusion conditions. Complement factors are being considered as targets for therapeutic intervention Objective We here characterize ARGX-117, a humanized inhibitory monoclonal antibody against complement C2. Methods The mode-of-action

Background Autophagy plays an important role in causing inflammatory responses initiated by environmental pollutants and respiratory tract infection. Objective We sought to investigate the role of cockroach allergen-induced excessive activation of autophagy in allergic airway inflammation and its underlying molecular mechanisms. Methods Environmental allergen-induced autophagy was investigated in the

Background Physicians treating COVID-19 patients increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across the spectrum of COVID-19 have not been characterized compared to healthy controls, but such analyses are likely to yield insights into the pursuit of interventions that adequately reduce the burden of these cytokine

Background There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) is currently available. Objective We propose new diagnostic criteria for ABPA/ABPM, consisting of ten components, and compare its sensitivity and specificity to existing methods

Background ILC2s are the dominant innate lymphoid cell population in the lungs at steady state and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity (AHR). Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210). Objective We characterized the effector functions of ILC210s

The humoral immune response provides specific, long-lived protection against invading pathogens, via immunoglobulin production and other memory functions. IgG, the most abundant immunoglobulin isotype, has the longest half-life and protects against bacterial and viral infections. The neonatal Fc receptor (FcRn) transports IgG across barriers, for example, the placenta, enhancing fetal humoral immunity

The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology. These molecules accelerate the destruction of IgG, reducing pathogenic IgG and IgG immune

Since the first description of the administration of high doses of pooled serum IgG, also referred to as intravenous IgG (IVIg) therapy, as being able to ameliorate various autoimmune diseases, researchers have been investigating which molecular and cellular pathways underlie IVIg activity. Apart from trying to understand the obvious conundrum that IgG can trigger both autoimmune pathology and resolution

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited constitutional symptoms to a hyperinflammatory state (“cytokine storm”) followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated

Background NGS has become a first-line tool for diagnosis of PID. However, patient access remains limited due to restricted insurance coverage and a lack of guidelines addressing use of targeted panels vs WES. Objectives To compare targeted next generation sequencing (NGS) with whole exome sequencing (WES) in a global population of patients with primary immunodeficiency (PID). Methods This is a longitudinal

Background Little is known about genetic determinants of severe asthma exacerbations. Objectives We aimed to identify genetic variants associated with asthma hospitalizations. Methods Genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, of whom 1,658 (cases) had at least one asthma-related hospitalization. This analysis was conducted using logistic regression

Objectives To identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. Background We studied two unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed Multisystem Inflammatory Syndrome in Children (MIS-C) in the setting of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Background The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts. Objective To develop consensus definitions for clinically relevant anaphylaxis outcomes utilizing a multidisciplinary group of clinical and research experts in anaphylaxis. Methods Using Delphi methodology

Metabolic inflammation (metaflammation) is characteristic of obesity related metabolic disorders, associated with increased risk of developing Type 2 Diabetes (T2D), Non-Alcoholic Fatty Liver Disease (NAFLD) or cardiovascular disease (CVD). Metaflammation refers to a chronic, low-grade systemic inflammation, compared to classical transient and acute inflammatory responses of the innate immune system

Medical advances have dramatically improved the long-term prognosis of children and adolescents with Inborn Errors of Immunity (IEIs). Transfer of medical care of individuals with pediatric IEIs to adult facilities is a complex task also for the high number of distinct disorders, that requires involvement of patients and both pediatric and adult care providers. To date, there is no consensus on the

Background Non-steroidal anti-inflammatory drugs exacerbated respiratory disease (N-ERD) asthma is characterized by chronic rhinosinusitis and intolerance to aspirin and other cyclooxygenase-1 inhibitors. Clinical data point to a heterogeneity within N-ERD phenotype. Objectives To investigate immune mediator profiles in lower airways of patients with N-ERD. Methods Levels of cytokines (luminex) and

Background There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of the coronavirus disease (COVID-19). Objective 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 (admission

Given the burden of disease and the consequences of a diagnosis of peanut allergy, it is important that peanut allergy be accurately diagnosed so that an appropriate treatment plan can be developed. However, a test that indicates there is peanut sensitization present (e.g., a “positive” test) is not always associated with clinical reactivity. This practice parameter addresses the diagnosis of IgE mediated

Background The immunoinhibitory receptor Siglec-8 on the surface of human eosinophils and mast cells binds to sialic acid-containing ligands in the local milieu resulting in eosinophil apoptosis, inhibition of mast cell degranulation and suppression of inflammation. Siglec-8 ligands were found on postmortem human trachea and bronchi and on upper airways in two compartments, cartilage and submucosal

Background Chr17q12-21.2 region is the strongest and most consistently associated region with asthma susceptibility. The functional genes or single nucleotide polymorphisms (SNPs) are not obvious due to linkage disequilibrium. Objectives Whole-genome sequence and RNAseq from human bronchial epithelial cells (BEC) were comprehensively investigated to dissect functional genes/SNPs for asthma severity

Background Peanut allergy is characterized by the development of IgE against peanut antigen. bjective Evaluate the evolution of epitope-specific (es)IgE and esIgG4 in a prospective cohort of high-risk infants to determine if antibody profiles can predict peanut allergy after 4 years of age. Methods The endpoint was allergy status at 4+ years; samples from 293 children were collected at 3-15 months

Background Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms

Background The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens. Objectives

Background Several underlying conditions have been associated with severe SARS-CoV2 illness, it remains unclear if underlying asthma is associated with worse COVID-19 outcomes. Objective Given the high prevalence of asthma in the New York City area, our objective was to determine if underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 disease compared

The NF-κB signaling system, a key regulator of immunological 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 hormones such as insulin

Chimeric antigen receptor T cells (CAR T) are a new and exciting immunotherapeutic approach to manage cancer, with impressive efficacy but potentially life threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation

Over 3 decades, gene therapy has advanced from a logical idea to becoming a clinical reality for several of the most severe primary immune deficiencies, as well as other inherited disorders. The first gene therapy medicines have been licensed for marketing and several more are advancing toward that goal to make them widely available, beyond clinical trials. Although common platforms of cells, vectors

Food allergy is a major health problem affecting 5% to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the US Food and Drug Administration. The only options were avoidance of food allergen triggers and acute

The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19–induced

Background The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. Objective The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major

Background More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. Objective We sought to identify and characterize subsets of

Background Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with CVID, but the optimal treatment is unknown. Objective Determine if rituximab with azathioprine or mycophenolate mofetil improves the HRCT of the chest and/or PFTs in patients with CVID and GLILD. Methods A retrospective chart review was performed of clinical and laboratory

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 To conduct a nationwide U.S. survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy. Methods Survey invitations were delivered to

Background Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Since the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. Objective To develop a model able to predict the risk of fatal outcome in COVID-19 patients, which could be used easily upon arrival of patients to the hospital. Methods We constructed

Anaphylaxis is a life-threatening allergic reaction caused by cross-linking of high-affinity IgE antibodies on the surface of mast cells and basophils. Understanding the cellular mechanisms that lead to high-affinity IgE production is required to develop better therapeutics for preventing this severe reaction. A recently discovered population of T follicular helper Tfh13 cells regulates the production

Asthma is a heterogeneous respiratory disease reflecting distinct pathobiological mechanisms. These mechanisms are based, at least partly, on different genetic factors shared by many other conditions, such as allergic diseases and obesity. Investigating the shared genetic effects enables better understanding the mechanisms of phenotypic correlations and is less subject to confounding by environmental

Background The upper airways present a barrier to inhaled allergens and microbes, which alter immune responses and subsequent risk for diseases, such as allergic rhinitis (AR). Objective We tested the hypothesis that early life microbial exposures leaves a lasting signature in DNA methylation that ultimately influences the development of AR in children. Methods We studied upper airway microbiota at