Asthma has been increasingly recognized as a heterogeneous disease; however, many patients with asthma suffer from allergic asthma. While inhaled corticosteroids and other inhalers have been integral in treating many symptoms of asthma, these medications do not completely address the underlying mechanism of the disease. Pediatric asthma imposes a substantial burden on patients and the healthcare system

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition characterized by type 2 (T2) immune responses with significant impacts on quality of life and healthcare costs. Local IgE production in nasal polyp tissue plays a key role in the T2 inflammatory cascade. Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment for some patients with CRSwNP regardless

The epidemiology of COVID-19 in children has evolved throughout the pandemic, with initially low infection rates rising significantly due to the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting SARS-CoV-2 infection. The immune response in children leads to milder

BACKGROUND IgG can mediate murine and human systemic anaphylaxis (SA). The roles of mast cells (MCs) and histamine in IgG-mediated anaphylaxis are controversial for mice and have not been studied in vivo for humans. We now investigate these issues. METHODS Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by i.v. antigen challenge. Anaphylaxis

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age

BACKGROUND An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD. OBJECTIVE To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses. METHODS Latent class trajectory analysis was

Self-reported food allergies (FAs) affect approximately 8% of the US pediatric and approximately 10% of the adult population, which reflects potentially disproportionate increases among ethnically and racially minoritized groups. Multiple gaps and unmet needs exist regarding FA disparities. There is reported evidence of disparities in FA outcomes, and the FA burden may also be disproportionate in low-income

BACKGROUND The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens, and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and

Immune responses require complex, spatially-coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualise a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments

BACKGROUND Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD). OBJECTIVE This trial evaluated the efficacy and safety of amlitelimab in adults with AD. METHODS In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NPs) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear. OBJECTIVE To reveal the roles

BACKGROUND The mental health conditions of allergic diseases has been investigated, but the consistency and magnitude of their effects are unclear. The aim of this umbrella review is to systematically evaluate the published evidence on allergic diseases and mental health conditions to establish a new hierarchy of evidence and identify gaps in this area of research. METHODS We systematically searched

BACKGROUND Ataxia Telangiectasia (A-T) is a DNA repair disorder with cancer predisposition. OBJECTIVE Characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T. METHODS Data was retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios

BACKGROUND Therapies targeting interleukin-5 (IL-5) or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma. OBJECTIVE To investigate the impact of anti-IL-5 and anti-IL-5Rα biological therapies on mast cells (MCs) and their progenitors. METHODS Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow, and in human

BACKGROUND There have been multiple reports of the anti-IL4Rα agent, dupilumab, as associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL). OBJECTIVE We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate possible underlying mechanism(s) for the potential association. METHODS First, we used the FDA pharmacovigilance database, FAERS

BACKGROUND T helper 2 (Th2) cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet, the upstream regulators that activate Th2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of Th2 cells as it is implicated in AD pathogenesis and has the capacity to activate T cells. OBJECTIVE To decipher the role of IL-18 in

Food Protein-Induced Enterocolitis (FPIES) is a non-IgE mediated GI food allergy characterized by delayed, protracted vomiting, accompanied by lethargy and pallor, usually 1-4 hours following ingestion of the food allergen. The pathophysiology of FPIES remains unknown and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last two decades,

BACKGROUND Clinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. OBJECTIVE We thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. METHODS

Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item

BACKGROUND CD19-targeted chimeric antigen receptor T-cell therapy (CAR-T therapy) has revolutionized the treatment of hematologic malignancies. As these cells target CD19+ receptors on B-cells, there is the potential for B-cell aplasia and hypogammaglobulinemia. Data on the degree and clinical significance of hypogammaglobulinemia are sparse. OBJECTIVE To evaluate hypogammaglobulinemia after CD19-targeted

BACKGROUND Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut. OBJECTIVE We sought to determine whether those who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific (es-) IgE profiles than those who achieved transient desensitization

BACKGROUND Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score (NPS), symptom and quality of life scores in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary care centres. METHODOLOGY NPS, SinoNasal Outcome Test (SNOT)-22 score, visual

BACKGROUND Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions often triggered by medications. While the involvement of CD8+ T cells causing keratinocyte death is well recognized, the contribution of neural elements to the persistent skin inflammation has been largely overlooked. OBJECTIVE To investigate the potential neuroimmune regulation in

BACKGROUND Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the presence of pathogenic autoantibodies and a substantial influx of immune cells into skin lesions. However, the role of eosinophils in BP remains inadequately elucidated. OBJECTIVE We sought to determine the pathologic involvement of eosinophils and eosinophil extracellular traps (EETs) in BP. METHODS Human samples

BACKGROUND It is thought that patients with inborn errors of immunity (IEI) are more susceptible to severe coronavirus disease 2019 (COVID-19) than the general population, but a quantification of this potential risk is largely missing. OBJECTIVE We assessed the impact of COVID-19 on patients with IEI. METHODS A nationwide cohort study was performed to estimate the relative risk (RR) for hospitalization

Asthma is a chronic lung condition that may be affected by numerous medical comorbidities. Such comorbidities can influence the presentation and even the severity of asthma. Alternatively, asthma may be misdiagnosed as a comorbidity when symptoms overlap. Three medical conditions that commonly affect asthma management are gastroesophageal reflux disease (GERD), laryngopharyngeal reflux (LPR), and vocal

BACKGROUND Cytokine storm syndromes (CSSs), including hemophagocytic lymphohistiocytosis (HLH), are increasingly recognized as hyperinflammatory states leading to multiorgan failure and death. Familial HLH in infancy results from homozygous genetic defects in perforin-mediated cytolysis by CD8 T lymphocytes and natural killer (NK) cells. Later-onset CSSs are often associated with heterozygous defects

BACKGROUND Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment. OBJECTIVE We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits,

BACKGROUND Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated constitutively activated mast cells (MCs) that release MC mediators, which might act on the tumor microenvironment including other immune cells. OBJECTIVE To investigate the blood distribution of B-cell, plasma cell (PC), and antibody isotype compartments in patients with SM. METHODS We used

BACKGROUND Acute exacerbations of chronic rhinosinusitis (AECRS) are commonly triggered by rhinovirus (RV) infections with secondary bacterial infections. Risk factors for AECRS are not well understood. OBJECTIVE We sought to determine whether carriers of the minor allele rs6967330 (AA/AG) in the cadherin-related family member 3 (CDHR3) gene have an increased risk for RV infections in AECRS in vivo

BACKGROUND IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4+ T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct. OBJECTIVE To identify CD4+ T cell differences between EoE and MA that may be responsible for distinct disease manifestations

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling cascade is an evolutionarily conserved signal transduction pathway that regulates many vital cellular processes, including immune function and hematopoiesis. Human genetic variants that disrupt JAK-STAT signaling are being found to cause a rapidly increasing number of diseases, including both germline-encoded inborn

BACKGROUND Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up. OBJECTIVE This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD. METHODS The study included US patients with COPD who

Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune

BACKGROUND The role of air pollution in eczema and food allergy development remains understudied. OBJECTIVE We aimed to assess whether exposure to air pollution is associated with eczema and food allergies in the first 10 years of life. METHODS HealthNuts recruited a population-based sample of 1-year-old infants who were followed up at ages 4, 6, and 10 years. Annual average fine particulate matter

BACKGROUND Patients with eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite histologic remission. OBJECTIVE We characterized persisting molecular alterations in pediatric patients with EoE using tissue transcriptomics

BACKGROUND Atopic dermatitis (AD) is an inflammatory skin condition characterized by widely variable cutaneous Staphylococcus aureus abundance that contributes to disease severity and rapidly responds to type 2 immune blockade (ie, dupilumab). The molecular mechanisms regulating S aureus levels between AD subjects remain poorly understood. OBJECTIVE We investigated host genes that may be predictive

Tissue ecosystems are cellular communities that maintain set points through a network of intercellular interactions. We position health and chronic inflammatory disease as alternative stable set points that are (1) robust to perturbation and (2) capable of adaptation and memory. Inflammatory memory, which is the storage of prior experience to durably influence future responsiveness, is central to how

Cough and itch are protective mechanisms in the body. Cough occurs as a reflex motor response to foreign body inhalation, while itch is a sensation that similarly evokes a scratch response to remove irritants from the skin. Both cough and itch can last for sustained periods, leading to debilitating chronic disorders that negatively impact quality of life. Understanding the parallels and differences

BACKGROUND Chronic rhinitis symptoms cause significant health burden among children and can have a heterogeneous presentation. Defining phenotypes of childhood chronic rhinitis and associated pathobiology may lead to prevention or improved treatments. OBJECTIVES We sought to identify longitudinal patterns of rhinitis symptoms in childhood and determine their associations with early life risk factors

Trained immunity has emerged as a new concept in immunology that is associated with the memory of innate immune cells and linked to specific metabolic and epigenetic reprogramming of these cells. Trained immunity may confer nonspecific and sustained protection against a broad range of pathogens, and recent findings show that it might also be involved in allergy mechanisms. Some conventional vaccines

Congenital athymia is a life-limiting disorder due to rare inborn errors of immunity causing impaired thymus organogenesis or abnormal thymic stromal cell development and function. Athymic infants have a T-lymphocyte-negative, B-lymphocyte-positive, natural killer cell-positive immunophenotype with profound T-lymphocyte deficiency and are susceptible to severe infections and autoimmunity. Patients

BACKGROUND Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine panels are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited. OBJECTIVE We sought to analyze real-world single-center use of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and