BACKGROUND Chronic erythroderma is a potentially life-threatening condition that can be caused by a variety of diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options. OBJECTIVE To establish a molecular disease map of chronic idiopathic erythroderma. METHODS We performed single-cell RNA sequencing combined with T-cell receptor sequencing of blood and skin

RATIONALE Approximately 85% Hereditary angioedema (HAE) attacks are associated with prodromal symptoms. We investigated the clinical effect of treating HAE-C1 inhibitor (HAE-C1INH) Type 1 patients with Conestat Alfa® (recombinant human C1-INH) during their prodrome versus an active swelling episode and associated changes in blood transcriptomic genes and pathways pre- vs. post-treatment. METHODS A

BACKGROUND Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life-limiting, but the mortality of CSU has not been investigated. OBJECTIVE To assess all-cause mortality in CSU patients, risk for comorbidities that are leading causes of death and impact of guideline-recommended urticaria treatments on mortality rates. METHODS This is a retrospective population-based

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies, demonstrating significant clinical efficacy and leading to FDA approval of several CAR-T cell-based products. This success has prompted exploration of CAR-T cell therapy in other disease areas, including autoimmune diseases (AIDs). CAR-T cells targeting B cells have been shown to provide

BACKGROUND Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of PLCG2 cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (PLAID-CU) is caused by in-frame deletions of PLCG2 that are dominant

BACKGROUND Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations. OBJECTIVES We sought to characterize gut microbiota in children using an enterotyping approach and determine

BACKGROUND Allergic diseases are major causes of morbidity in both developed and developing countries and represent a global burden on health care systems. Allergic sensitization is defined as the production of immunoglobulin E (IgE) specific to common environmental allergens, and it is an important indicator in the assessment of allergic diseases. OBJECTIVES This study aimed to clarify the genetic

BACKGROUND STAT3 gain-of-function (GOF) disease presents with lymphoproliferation, autoimmunity, and failure to thrive. While JAK inhibitors have alleviated symptoms, their effects on disease pathogenesis remain unclear. OBJECTIVE We prospectively investigated the clinical, immunological, and transcriptomic responses of four STAT3 GOF patients under long-term ruxolitinib treatment. METHODS We conducted

BACKGROUND CD4+ T cells play essential roles in adaptive immunity. Distinct CD4+ T cell subsets - Th1, Th2, Th17, Th22, T follicular helper and regulatory T cells - have been identified and their contributions to host defence and immune regulation are increasingly well-defined. IL-9 producing Th9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity

BACKGROUND Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). OBJECTIVE We aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. METHODS We recruited children who presented to the emergency room

BACKGROUND Inborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the

BACKGROUND Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE associated tissue remodeling causes clinical dysphagia, food impactions

Aerosolized particles with a biological origin are called bioaerosols. Bioaerosols from plants, animals, fungi, bacteria and viruses are an important class of environmental exposures that are clinically relevant to asthma. However, there are important differences in the pathways by which various bioaerosols impact asthma. Additionally, differences in individual susceptibility to different bioaerosols

BACKGROUND Airway hyper-responsiveness (AHR) is a hallmark of persistent asthma. However, effects of IL-4/13 blockade with dupilumab (Dupi) on AHR are unknown. OBJECTIVE To investigate the effect of 12 weeks of Dupi on AHR, asthma control and quality of life. METHODS After a 4-week run-in on beclomethasone/formoterol(BDP/FM) MART (baseline), participants with uncontrolled type-2 high severe asthma

The major challenge in allergy diagnosis is development of accessible and reliable diagnostics that can predict the clinical outcome following exposure to culprit allergen(s) or cross-reactive molecules and identification of safer alternatives than the current state-of-the-art methods. There is accumulating evidence that flow-based analyses for the quantification of activated basophils and mast cells

BACKGROUND Exposure to fungi, especially Aspergillus fumigatus (A.f.), can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs), initiate allergic inflammatory responses to allergic stimuli. However, it is unclear if A.f. spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required

BACKGROUND In addition to FcεRI, a subtype of human mast cells (MCs) expresses Mas-related G-protein coupled receptor X2 (MRGPRX2, mouse counterpart MrgprB2). Although MrgprB2 contributes to IgE-mediated passive systemic anaphylaxis (PSA) in vivo, an MRGPRX2 inhibitor (C9) does not block MrgprB2-mediated or IgE-mediated MC degranulation in vitro. OBJECTIVE To generate mice expressing human MRGPRX2

Laboratory-based immunology evaluation is essential to the diagnostic work-up of patients with complex immune disorders, and is as essential, if not more so, depending on the context, than genetic testing, as it enables identification of aberrant pathways amenable to therapeutic intervention, and clarifies variants of uncertain significance. There have been considerable advances in techniques and instrumentation

BACKGROUND Airway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. OBJECTIVE We investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. METHODS We assessed associations between body mass index and airway

Omalizumab was recently approved by the US Food and Drug Administration for treatment of any single food allergy or multiple food allergies in children aged 1 year and older and adults. There is currently no formal guidance regarding recommended best practices for omalizumab use in food allergy, including patient selection, anticipated goals and outcomes of therapy, procedure for monitoring patients

BACKGROUND Melatonin has been reported to relieve the inflammatory symptoms and improve sleep disturbance in AD patients. Recent studies showed that melatonin exerted beneficial actions by remodeling intestinal microbiota composition; however, whether the beneficial effects of melatonin in AD were mediated by the modulation of skin microbiota remains unclear. OBJECTIVE We sought to investigate the

BACKGROUND Psychological stress can exacerbate the development of allergies; however, the underlying mechanisms remain poorly understood. IgE-mediated cutaneous allergic inflammation (IgE-CAI) is a basophil-dependent skin allergy with eosinophil infiltration at inflammatory sites. Its resolution involves anti-inflammatory programmed death ligand 2 (PD-L2)-positive macrophages. OBJECTIVE This study

BACKGROUND Respiratory disease is a frequent cause of morbidity and mortality in common variable immunodeficiencies (CVIDs); however, lung function trajectories are poorly understood. OBJECTIVE We sought to determine lung physiology measurements in CVIDs, their temporal trajectory, and their association with clinical and immunologic parameters. METHODS This retrospective study from 5 Italian centers

The epidemiology of coronavirus disease 2019 (COVID-19) in children has evolved throughout the pandemic, with initially low infection rates rising significantly as a result of 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 severe acute respiratory syndrome

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

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 are now investigating these issues. METHODS Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by intravenous antigen challenge

BACKGROUND Inflammation is a double-edged state of immune activation that is required to resolve threats harmful to the host, but can also cause severe collateral damage. Polymorphonuclear neutrophils (PMNs), the primary leukocyte population in humans, mediate inflammation through the release of cytokines and neutrophil extracellular traps (NETs). Although the pathophysiological importance of NETs

BACKGROUND Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied. OBJECTIVES Our aim was to gain insight into microbiome-mediated defenses and respiratory

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 We sought to determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms on the basis of multiomics analyses. METHODS Latent class trajectory

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-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote

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 (NP) 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

Immune responses require complex, spatially coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualize 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 mAb 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 (ClinicalTrials.gov identifier NCT05131477), patients

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

BACKGROUND The mental health conditions of allergic diseases have been investigated, but the consistency and magnitude of their effects are unclear. The aim of this umbrella review was 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 Therapies targeting IL-5 or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma. OBJECTIVE We sought 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 lungs and

BACKGROUND There have been multiple reports of the anti-IL-4Rα agent, dupilumab, being 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 the possible underlying mechanism or mechanisms for the potential association. METHODS First, we used the Food and Drug

BACKGROUND 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 because it is implicated in AD pathogenesis and has the capacity to activate T cells. OBJECTIVE We sought 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 benefits of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exist regarding the impact of mepolizumab on airway remodeling. OBJECTIVE We sought to investigate the effect of mepolizumab on airway structural remodeling in patients treated for severe asthma in routine clinical care

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 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 patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization

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. OBJECTIVES We sought to evaluate hypogammaglobulinemia after

BACKGROUND Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score 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 centers. METHODOLOGY Nasal polyp score, Sinonasal Outcome Test 22 score

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 We investigated the potential neuroimmune regulation