BACKGROUND Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. OBJECTIVE To compare the effects of monoclonal antibodies and ASA desensitization (ASA-D) for treatment of CRSwNP. METHODS We searched MEDLINE, EMBASE, CENTRAL, ICTRP, FDA and EMA databases from inception to Aug 4, 2021 for RCTs comparing the effects of monoclonal

Background Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia

Background Asthma is a heterogenous disease. Clinical blood parameters differ by race/ethnicity and are used to distinguish asthma subtypes and inform therapies. Differences in subtypes may explain population-specific trends in asthma outcomes. However, these differences in racial/ethnic minority pediatric populations are unclear. Objective Investigate the association of blood parameters and asthma

Background Epidemiological studies have shown that Alzheimer’s disease and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. Objective To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (p-Tau181)

Background Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. Objective By leveraging data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) and the Atopic Dermatitis

Background Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection. Objective To evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time. Methods SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent

Background Inborn errors of immunity (IEI) are genetic disorders characterized by various degrees of immune dysregulation that can manifest as immune deficiency, autoimmunity or autoinflammation. The routine use of next-generation sequencing in the clinic has facilitated the identification of an ever-increasing number of IEI, revealing the roles of immunologically important genes in human pathologies

Background The risk factors determining short- and long-term morbidity following acute respiratory infection (ARI) due to respiratory syncytial virus (RSV) in infancy remain poorly understood. Objectives To examine the associations of the upper respiratory tract (URT) microbiome during RSV ARI in infancy with the acute local immune response and short- and long-term clinical outcomes. Methods We characterized

IgY, the avian homolog to mammalian IgG, has therapeutic potential as an orally absorbed, transmucosally excreted, antigen-specific antibody. A new cat food product, admixed with anti-Fel d 1 IgY derived from hyperimmunized hen egg yolks, is intended to treat allergic rhinitis indirectly via specific neutralization of Fel d 1. Polyclonal IgY as a trans-species oral passive immunization modality offers

Background The extent to which asthma-related ED visit incidence rates vary from neighborhood to neighborhood and predictors of neighorbood-level asthma ED visit burden are not well understood. Objective To describe the census tract-level spatial distribution of asthma-related emergency department visits in Central Texas and identify neighborhood-level characteristics that explain variability in neighborhood-level

Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus marked by eosinophilic infiltration. Cumulative evidence indicates that the risk of EoE involves the complex interplay of both genetic and environmental factors. As only a few genetic loci have been identified in EoE, the genetic underpinning of EoE remains largely elusive. Objective We aimed to identify genetic

Background The most common endotype of asthma is Type 2 high asthma, which is sometimes driven by adaptive allergen-specific Th2 lymphocytes that react to allergens presented by dendritic cells (DCs), or sometimes by an innate immune response dominated by type 2 innate lymphocytes (ILC2s). Understanding the underlying pathophysiology of asthma is essential to improve patient tailored therapy. The STE20

Background CD25+ human mast cells (huMCs) have been reported in patients with monoclonal mast cell diseases and in rare association with inflammation. However, the regulation of CD25 expression on huMCs and the possible biologic consequences remain poorly understood. Objective We sought to identify conditions which would up-regulate CD25 expression on huMCs and to explore possible functional implications

Background SARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEI); however, little is known about immunogenicity and safety in these patients. Objectives To evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse event (AE) in a cohort of patients with IEI. Methods Plasma was collected from twenty-two

Background The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions. Objective As FcεRI-expressing mast cell progenitors are the dominating mast cell type

Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis are associated with adverse pregnancy outcomes. Active maternal disease during pregnancy is associated with additional negative outcomes. Anti-TNF agents are effective treatments for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis

Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant’s risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow’s milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and

In addition to being a source of nutrients for the developing newborn, human milk contains thousands of bioactive compounds, which influence infant health in the short-term as exemplified by its major benefits on infectious disease prevention. Many of the human milk compounds also have the required characteristics to instruct immune development and guide long-term health. Prebiotics, probiotics, and

Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high heritability. Previous genome-wide association studies (GWASs) have identified several loci predisposing to AD. These findings explain ∼30% of the variance in AD susceptibility suggesting that further work is required to fully understand the genetic underpinnings. Objective To gain additional understanding of

JAK inhibitors (JAKi) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKi can block the signalling activity of a variety of pro-inflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKi are licensed and many more undergoing

Atopic dermatitis is a chronic inflammatory skin disorder associated with heterogenous presentation and often immense patient burden. Safe, targeted treatment options are currently limited. We conducted a focused review of the published literature, including clinical trial results, case reports, and abstracts, as well as presentations from scientific meetings and data from industry press releases,

Inborn errors of immunity (IEIs) are traditionally best known for enhanced susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in IEIs. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize

Background House dust mite (HDM) allergens are major elicitors of allergic reactions worldwide. Objective Identification, characterization and evaluation of diagnostic utility of new important HDM allergens. Methods A cDNA coding for a new Dp allergen, Der p 37, was isolated from a Dp expression library with allergic patients IgE antibodies. Recombinant Der p 37 expressed in Escherichia coli was purified

Background Acute increases of ≥20%+2 ng/mL (20+2 rule) over basal serum tryptase (BST) is the recommended threshold supporting a clinical diagnosis of anaphylaxis. Prospective studies have demonstrated high sensitivity for this algorithm following parenteral exposures, but specificity has not been evaluated. Objective To define a serum tryptase change that distinguishes baseline variability from anaphylaxis

Background Clinical management of allergic diseases has been hampered by the lack of safe and convenient tests to reliably identify culprit allergens and to closely follow changes in disease activity over time. Since allergy diagnosis is a complex and laborious multistep procedure, there is an urgent need for simpler but still functionally accurate ex vivo assays allowing objective diagnosis, substantiating

Background Mechanical alloknesis (or innocuous mechanical stimuli–evoked itch) often occurs in dry skin–based disorders such as atopic dermatitis and psoriasis. However, the molecular and cellular mechanisms underlying mechanical alloknesis remain unclear. We recently reported the involvement of CD26 in the regulation of psoriatic itch. This molecule exhibits dipeptidyl peptidase IV (DPPIV) enzyme

Background Proteasome associated auto-inflammatory syndromes (PRAAS) form a family of recently described rare autosomal recessive disorders of disturbed proteasome assembly and proteolytic activity caused by mutations in genes coding for proteasome subunits. Treatment options for these proteasome disorders consist of life-long immunosuppressive drugs or JAK inhibitors, which may have partial efficacy

Background Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib+TCS in patients with moderate-to-severe AD. Objective Evaluate efficacy and safety of UPA+TCS through 52 weeks. Methods Patients (12-75y) with chronic AD (≥10% of body surface area affected, EASI ≥16, vIGA-AD™ ≥3, and WP-NRS score ≥4) were

Background Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. Objective To systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact

Mast cells and eosinophils are commonly found, expectedly or unexpectedly, in human tissue biopsies. Although the clinical significance of their presence, absence, quantity, and quality continues to be investigated in homeostasis and disease, there are currently gaps in knowledge related to what constitutes quantitatively relevant increases in mast cell and eosinophil number in tissue specimens for

Background Development of a diverse T cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for SCID. High-throughput sequencing (HTS) of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution. Objectives We investigated whether longitudinal analysis of the TRB repertoire would accurately describe TCR

Background Eosinophilic esophagitis (EoE) is a histologically “patchy” disease with uneven eosinophil distribution along the esophagus, posing a dilemma for histologically analyzing endoscopic biopsies, especially when biopsies are limited to only the distal esophagus. Objective We investigated whether molecular mRNA profiling of a distal esophageal biopsy predicts eosinophilia in the proximal esophagus

Background Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality. Objective The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen(s) for HLH disorders. Methods Included are 261 patients with HLH disorders transplanted

Background Symptomatic Dermographism (SD) is the most common form of Chronic Inducible Urticaria (CIndU). The gold standard for diagnosing SD and disease activity assessment in SD is provocation testing. As of now, if and what cofactors impact on provocation test results is unknown. Objective To determine if the induction of signs and symptoms of SD is affected by the intake of food. Methods We performed

Background Mast cells (MCs) are considered the main effectors in allergic reactions and well known for their contribution to the pathogenesis of various inflammatory diseases, urticaria and mastocytosis. To study their functions in vitro, human primary MCs are isolated directly from several tissues or differentiated from hematopoietic progenitors. However, these techniques bear several disadvantages

Background Currently, there are no approved therapies to treat congenital athymia, a condition of immune deficiency resulting in high early mortality due to infection and immune dysregulation. Multiple syndromic conditions, such as complete DiGeorge syndrome, 22q11.2 deletion syndrome, CHARGE (coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies

Aspirin-exacerbated respiratory disease (AERD) is a condition composed of chronic rhinosinusitis with nasal polyposis and asthma that is defined by respiratory hypersensitivity reactions to the cyclooxygenase 1–inhibitory effects of nonsteroidal anti-inflammatory drugs. It is diagnosed in 5% to 15% of patients with asthma and is even more common in those with comorbid nasal polyposis. Diagnosis is

Aspirin-exacerbated respiratory disease (AERD) is a complex inflammatory disorder that is not generally viewed as a disease involving the adaptive immune system but instead one largely driven by the innate immune system. This article focuses on the cellular dysregulation involving 4 central cell types: eosinophils, basophils, mast cells, and innate lymphoid type 2 cells. AERD can be envisioned as involving

Background A major issue with the current management of psoriasis is our inability to predict treatment response. Objective Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for psoriatic patients. Methods We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles

Background IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (AGS) delayed anaphylaxis after ingestion of mammalian meat. Development of sensitization has been attributed to tick bites, however the possible role of other parasites has not been well studied. Objective We assessed presence, relative abundances, and site of localisation of alpha-gal containing proteins in common

Background Work exposures play a significant role in adult-onset asthma, but mechanisms of work-related asthma are not fully elucidated. Objective We aimed to reveal the molecular mechanisms of work-related asthma associated with flour (FA), isocyanate (IA) or welding fume (WA) exposures and identify potential biomarkers that distinguish these groups from each other. Methods We used a combination of

Background The thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence resulting in a severe reduction or absence of naïve T cell output. The ability to generate a patient derived human thymus would provide an attractive research platform and

Background Pediatric non-malignant lymphoproliferative disorders (PLPD) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. Objective The primary objective of this study was to ascertain the spectrum of genomic immunologic defects

Background Mast cells have a profound impact on allergic asthma. Under such conditions, mast cells undergo degranulation, resulting in the release of exceptionally large amounts of mast cell-restricted proteases. However, the role of these proteases in asthma is only partially understood. Objectives Here we hypothesized that the mast cell proteases can influence the functionality of human lung fibroblasts

Background Mast cells are involved in many distinct pathological conditions, suggesting that they recognize and respond to various stimuli and thus require a rich repertoire of cell surface proteins. However, mast cell surface proteomes have not been comprehensively characterized. Objective We aimed to further characterize the mast cell surface proteome to obtain a better understanding of how mast

Background Low epidermal filaggrin (FLG) is a risk factor for atopic dermatitis (AD) and allergic co-morbidity. FLG mutations do not fully explain the variation in epidermal FLG levels, highlighting that other genetic loci may also regulate FLG expression. Objective To identify genetic loci that regulate FLG expression and elucidate their functional and mechanistic consequences. Methods A genome-wide

Air pollutants are a major source of increased risk of disease, hospitalization, morbidity, and mortality worldwide. The respiratory tract is a primary target of potential concurrent exposure to both inhaled pollutants and pathogens, including viruses. While there are a variety of associative studies linking adverse outcomes to co- or subsequent exposures to inhaled pollutants and viruses, knowledge