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Allergology International : Official... Jan 2024Semaphorins were originally identified as guidance molecules in neural development. However, accumulating evidence indicates that 'immune semaphorins' are critically... (Review)
Review
Semaphorins were originally identified as guidance molecules in neural development. However, accumulating evidence indicates that 'immune semaphorins' are critically involved in regulating immune cell activation, differentiation, mobility and migration. Semaphorins are also intimately associated with the pathogenesis of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and eosinophilic chronic rhinosinusitis. Interestingly, reflecting their function in positive or negative regulation of immune cells, levels of some semaphorins are increased while others are decreased in patients with allergic diseases. This review presents the pathogenic functions of immune semaphorins in allergic inflammation and discusses the potential use of these molecules as therapeutic targets for allergic diseases.
Topics: Humans; Semaphorins; Asthma; Inflammation; Sinusitis
PubMed: 37635021
DOI: 10.1016/j.alit.2023.08.006 -
Investigative Ophthalmology & Visual... Jul 2023To explore the role of Th2 signaling pathway in allergic conjunctivitis (AC).
PURPOSE
To explore the role of Th2 signaling pathway in allergic conjunctivitis (AC).
METHODS
Serum Th2 cytokines IL-4 or IL-13 of patients with AC were detected using the Meso scale discovery assay to verify the correlation of Th2 immunity and AC pathogenesis. Wistar Han rats were intraperitoneally and subcutaneously injected with ovalbumin (OVA) to establish an experimental AC model and the Th2 signaling pathway was blocked by an investigational neutralizing antibody (CM310). Serum IgE and OVA-specific IgE were detected by ELISA. Conjunctivitis inflammation, infiltration of eosinophils, and mast cell degranulation were detected by histological examination. Immortalized human conjunctival epithelial cells, a conjunctival epithelial cell line, and peripheral blood mononuclear cells of patients with AC were used as the target cells to study the impact of IL-4 or IL-13 on AC progression. Finally, a STAT6 reporter gene system was constructed using immortalized human conjunctival epithelial cells to confirm whether the downstream signaling pathway activated by IL-4 or IL-13.
RESULTS
Serum IL-4 or IL-13 were increased in patients with AC versus healthy individuals. In an OVA-induced rat experimental AC model, blocking the Th2 signaling pathway with CM310, an investigational neutralizing antibody, alleviated the conjunctival symptoms, and decreased serum IgE, suppressed infiltration of eosinophils and mast cell degranulation. Further, an in vitro model showed CM310 suppressed the secretion of inflammatory cytokine from both immune cells and epithelial cells in both patients peripheral blood mononuclear cells and cell line.
CONCLUSIONS
Blocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in AC.
Topics: Humans; Rats; Animals; Mice; Conjunctivitis, Allergic; Interleukin-13; Interleukin-4; Leukocytes, Mononuclear; Rats, Wistar; Inflammation; Immunoglobulin E; Signal Transduction; Cytokines; Ovalbumin; Th2 Cells; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37486293
DOI: 10.1167/iovs.64.10.30 -
Cureus Dec 2023Allergic rhinitis (AR) is a chronic ailment triggered by immunoglobulin E (IgE)-mediated reactions to allergens. Generally, AR is accompanied by asthma and... (Review)
Review
Allergic rhinitis (AR) is a chronic ailment triggered by immunoglobulin E (IgE)-mediated reactions to allergens. Generally, AR is accompanied by asthma and conjunctivitis. The risk factors of AR include both inhalant and occupational allergens and genetic factors. Although AR is not a life-threatening condition, it poses a significant risk of morbidity and hampers work-related performance. Currently, the diagnosis of AR is based on clinical history and physical examination of the patients. Furthermore, several laboratory tests such as skin pricking test (SPT), nasal allergen challenge (NAC), and computed tomography (CT) are also recommended in some cases. Nasal cytology can aid in the differentiation of rhinitis because of allergy or infection. Apart from this, molecular diagnostic modalities such as basophil activation test (BAT) and Immune Solid-Phase Allergy Chip (ISAC) can also be employed for the confirmatory diagnosis of AR. Immunotherapy has demonstrated efficacy in the management of AR, with only mild side effects. With the advancement in the diagnostic realm of AR, personalized treatment approach has also gained significant popularity. Immunotherapy is gaining evidence on becoming a personalized treatment approach for the management of AR. This article provides a comprehensive overview, aiming to bridge the gap between evolving diagnostics and personalized therapeutic strategies for allergic rhinitis.
PubMed: 38292952
DOI: 10.7759/cureus.51370 -
Children (Basel, Switzerland) Sep 2023Allergic rhinitis is an important disease with a global footprint and a growing prevalence, affecting children and adults. Although it is commonly under-diagnosed and... (Review)
Review
Allergic rhinitis is an important disease with a global footprint and a growing prevalence, affecting children and adults. Although it is commonly under-diagnosed and under-treated, it causes important social and economic effects (diminished quality of life, poor academic performance, escalated medical visits, heightened medication usage, and effects in other chronic conditions, e.g., asthma). It is characterized by distinctive, easily identifiable symptoms (sneezing, nasal discharge, nasal congestion, nasal-eye-palatal itching) and indirect accompanying indicators (fatigue and decreased school performance). The classification of allergic rhinitis hinges upon its nature and chronic distribution (seasonal or perennial) and its intensity, which spans from mild to moderate and severe. The diagnostic process primarily relies upon recognizing key clinical indicators, evaluating historical records, and considering risk factors. It is supported by abnormal laboratory findings, like in vitro allergen-specific IgE tests (enzyme immunoassay-EIA, chemiluminense immunoassay-CLIA) or in vivo skin prick tests for specific allergens. In the differential diagnosis, other chronic diseases manifesting with chronic rhinitis should be excluded (e.g., rhinosinusitis, chronic non-allergic rhinitis, rhinitis triggered by medications). The treatment of allergic rhinitis in children is mainly chronic and is focused on allergen exposure prevention, drug therapy, and immunotherapy in severe cases. Locally administered intranasal corticosteroids are the cornerstone of therapy. They are safe, effective, and have a favorable safety profile even during long-term use. Choosing a suitable intranasal corticosteroid drug with low systemic bioavailability makes long-term treatment even safer. Combinations of intranasal corticosteroids and H1 antihistamines are available in several countries and are widely used in more severe cases and the presence of year-round symptoms. Adding newer-generation oral H1-antihistamines broadens the available therapeutic inventory without significant effects compared to using previous-generation, once widely available, H1-antihistamines. Treatment of allergic rhinitis is complex and multi-dimensional, requiring an effective approach by a specialized group of specialized pediatricians, and is severely affected by the concurrent presence or development of other diseases in the spectrum of allergic diseases (conjunctivitis, asthma).
PubMed: 37761533
DOI: 10.3390/children10091571 -
Investigative Ophthalmology & Visual... Dec 2023Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a...
PURPOSE
Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a noninflammatory condition, a number of recent studies have associated keratoconus (KC) with allergic conjunctivitis (AC) based on clinical parameters. This study aimed to consolidate this association by performing a proteomic analysis of tear fluid from patients with keratoconus and/or allergic conjunctivitis.
METHODS
Of 51 patients, 17 were diagnosed with KC, 17 were diagnosed with AC, and 17 were diagnosed with both KC and AC (combined). Nine of 34 patients with KC had a progressive form of the disease. Tear fluid samples (n = 51, one eye per patient) were collected by the Schirmer's strips. Tear proteins were extracted from the Schirmer's strips. Proteomic profiling of 384 inflammatory proteins was assessed by a multiplex proximity extension assay (Olink Explore 384 Inflammation Panel I).
RESULTS
A total of 384 inflammatory proteins were measured. Two hundred seventy-two of the 384 proteins passed stringent data cleaning and were compared among the patient groups. Compared to the 2 other groups, LGALS9 was upregulated uniquely in KC, whereas FGF19, PDGFB, HPCAL1, OSM, and FCAR were downregulated in KC. Similarly, TNFRSF4 and CCL13 were specifically upregulated in AC, whereas ectodysplasin A receptor (EDAR) was uniquely downregulated in AC.
CONCLUSIONS
High-throughput proteomic profiling of tear fluid confirms the association between KC and AC on a molecular level and raise the importance of redefining KC as an inflammatory condition.
Topics: Humans; Keratoconus; Conjunctivitis, Allergic; Proteome; Proteomics; Cornea; Tears
PubMed: 38064228
DOI: 10.1167/iovs.64.15.9 -
Clinical and Experimental Allergy :... Dec 2023Distinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we aimed to identify and validate cough...
INTRODUCTION
Distinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we aimed to identify and validate cough phenotypes based on measurable traits, physician diagnoses, and prognosis.
METHODS
We used data from the Swiss Paediatric Airway Cohort and included 531 children aged 5-16 years seen in outpatient clinics since 2017. We included children with any parent-reported cough (i.e. cough without a cold, cough at night, cough more than other children, or cough longer than 4 weeks) without current wheeze. We applied latent class analysis to identify phenotypes using nine symptoms and characteristics and selected the best model using the Akaike information criterion. We assigned children to the most likely phenotype and compared the resulting groups for parental atopy history, comorbidities, spirometry, fractional exhaled nitric oxide (FeNO), skin prick tests and specific IgE, physician diagnoses, and 1-year prognosis.
RESULTS
We identified four cough phenotypes: non-specific cough (26%); non-allergic infectious and night cough with snoring and otitis (4%); chronic allergic dry night cough with snoring (9%); and allergic non-infectious cough with rhino-conjunctivitis (61%). Children with the allergic phenotype often had family or personal history of atopy and asthma diagnosis. FeNO was highest for the allergic phenotype [median 17.9 parts per billion (ppb)] and lowest for the non-allergic infectious phenotype [median 7.0 parts per billion (ppb)]. Positive allergy test results differed across phenotypes (p < .001) and were most common among the allergic (70%) and least common among the non-specific cough (31%) phenotypes. Subsequent wheeze was more common among the allergic than the non-specific phenotype.
CONCLUSION
We identified four clinically relevant cough phenotypes with different prognoses. Although we excluded children with current wheeze, most children with cough belonged to allergy-related phenotypes.
Topics: Child; Humans; Latent Class Analysis; Snoring; Hypersensitivity; Hypersensitivity, Immediate; Phenotype; Cough; Respiratory Sounds; Nitric Oxide
PubMed: 37997173
DOI: 10.1111/cea.14416 -
Current Opinion in Allergy and Clinical... Oct 2023Atopic dermatitis (AD) and ocular allergy aka allergic eye disease (AED) are two common conditions that often coexist in patients. However, molecular connections between... (Review)
Review
PURPOSE OF REVIEW
Atopic dermatitis (AD) and ocular allergy aka allergic eye disease (AED) are two common conditions that often coexist in patients. However, molecular connections between these two conditions are incompletely understood. While common etiologic components including Th2 immune signaling have been suggested for AD and AED, the mechanism how current Th2-targetd therapies (dupilumab, tralokinumab) for AD can augment conjunctivitis is not well understood.
RECENT FINDINGS
Differentially regulated genes and pathways relevant for AD disease manifestation are known. In contrast, similar information is not yet available for AED, which could be largely addressed by emerging noninvasive ocular sampling techniques. Emerging evidence indicated a reduction in goblet cell number and mucin production in a subpopulation of AD patients with AD leading to adverse ocular outcomes, while other potential mechanisms could also be involved. Involvement of particular barrier function protein(s) in AED needs further investigation.
SUMMARY
Modern cytokine-targeted therapies for AD showed elevated risk for developing conjunctivitis. Recently developed noninvasive sampling techniques should be leveraged to identify AD endotypes associated with AED and with dupilumab-associated ocular outcomes.
Topics: Humans; Dermatitis, Atopic; Conjunctivitis
PubMed: 37527055
DOI: 10.1097/ACI.0000000000000931 -
The Science of the Total Environment Dec 2023Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and... (Review)
Review
Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and asthma. Outdoor aeroallergens are found predominantly in pollen grains and fungal spores, which are allergen carriers. Aeroallergens from pollen and fungi have seasonal emission patterns that correlate with plant pollination and fungal sporulation and are strongly associated with atmospheric weather conditions. They are released when allergen carriers come in contact with the respiratory system, e.g. the nasal mucosa. In addition, due to the rupture of allergen carriers, airborne allergen molecules may be released directly into the air in the form of micronic and submicronic particles (cytoplasmic debris, cell wall fragments, droplets etc.) or adhered onto other airborne particulate matter. Therefore, aeroallergen detection strategies must consider, in addition to the allergen carriers, the allergen molecules themselves. This review article aims to present the current knowledge on inhalant allergens in the outdoor environment, their structure, localization, and factors affecting their production, transformation, release or degradation. In addition, methods for collecting and quantifying aeroallergens are listed and thoroughly discussed. Finally, the knowledge gaps, challenges and implications associated with aeroallergen analysis are described.
Topics: Allergens; Pollen; Asthma; Particulate Matter; Europe; Air Pollutants
PubMed: 37709071
DOI: 10.1016/j.scitotenv.2023.167042 -
Current Allergy and Asthma Reports Jun 2024The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of... (Review)
Review
PURPOSE OF REVIEW
The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface.
RECENT FINDINGS
Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.
PubMed: 38869807
DOI: 10.1007/s11882-024-01150-0 -
Life (Basel, Switzerland) May 2024Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North... (Review)
Review
Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North Americans and 20% of the world's population are impacted by some form of allergy and it continues to increase in prevalence, especially among children. Specified IgE antibodies can be found in almost all cases of exposure to seasonal or perennial allergens. Activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins. The release of these factors initiates the recruitment of inflammatory cells in the conjunctival mucosa, which causes the late-phase reaction. Signs and symptoms of ocular allergies include itching, tearing, chemosis, and hyperemia, which can lead to decreased productivity and poor quality of life. Many treatment options are available to improve symptoms, including, mast cell stabilizers, antihistamines, dual-acting agents, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and other off-label treatment modalities. This review article provides an overview of different types of allergic conjunctivitis, its pathology and immunology, and recommended methods of treatment.
PubMed: 38929634
DOI: 10.3390/life14060650