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Frontiers in Allergy 2023Specific IgE (sIgE) is merely a sensitization marker that cannot be used for allergy diagnosis if there are no associated clinical symptoms. As of 2023, there is still...
INTRODUCTION
Specific IgE (sIgE) is merely a sensitization marker that cannot be used for allergy diagnosis if there are no associated clinical symptoms. As of 2023, there is still no evidence regarding the quantity of sIgE necessary to confirm or exclude clinical disease. Therefore, this study aimed to calculate cut-offs for sIgE, allowing us to effectively diagnose olive or grass pollen allergy and select allergenic immunotherapy (AIT) candidate patients in a region under high olive and grass allergenic pressure.
METHODS
An observational retrospective study consisting of the review of electronic medical records from 1,172 patients diagnosed with seasonal rhino-conjunctivitis and suspected allergy to olive or grass pollen. Symptoms correlated with sIgE to Poaceae and Oleaceae whole extracts and sIgE to genuine allergenic components were evaluated. Optimal cut-off values were calculated using receiver operating characteristic curves. Relevant clinical symptoms and AIT indications were taken into consideration when determining the clinical allergy diagnosis.
RESULTS
sIgE to Lolium showed the best area under the curve (AUC) for both diagnosis (0.957) and an indication of AIT (0.872). The optimal cut-off values for grass diagnosis and AIT indication were 1.79 kUA/L and 8.83 kUA/L, respectively. A value of 5.62 kUA/L was associated with a positive likelihood ratio (LR) of 10.08 set for grass allergy. Olea sIgE showed the best AUC for the diagnosis (0.950). The optimal cut-off for diagnosis was 2.41 kUA/L. A value of 6.49 kUA/L was associated with a positive LR of 9.98 to confirm olive pollen allergy. In regard to immunotherapy, Ole e 1 sIgE showed the best AUC (0.860). The optimal cut-off was 14.05 kUA/L. Ole e 1 sIgE value of 4.8 kUA/L was associated with a 0.09 negative LR to exclude olive AIT indication.
CONCLUSIONS
The sIgE cut-offs found in this population under high olive and grass allergenic pressure reduce the gap between sensitization and clinical allergy, providing a new tool for the diagnosis of seasonal allergic rhinitis/asthma and helping to discriminate patients who will benefit from AIT.
PubMed: 37859976
DOI: 10.3389/falgy.2023.1241650 -
Frontiers in Pediatrics 2023This case report describes two cases of unilateral limbal Vernal keratoconjunctivitis (VKC) in the same family. To our knowledge, these are the first two reported cases...
This case report describes two cases of unilateral limbal Vernal keratoconjunctivitis (VKC) in the same family. To our knowledge, these are the first two reported cases of unilateral limbal VKC. VKC is a chronic inflammatory disease that typically affects both eyes, with unilateral cases being rare and previously only reported in the tarsal form. Our first case involved a 12-year-old girl with a history of allergic asthma, who had been experiencing conjunctivitis in her right eye since the age of 7. Upon examination, she was diagnosed with unilateral limbal VKC and treated with 1% cyclosporine eye drops with a significant improvement observed at the one and three-month follow-ups. Her 7-year-old brother was also examined and found to have unilateral limbal VKC in his right eye, although it was milder and not associated with allergic pathogenesis. Therefore, in this case, a treatment with hydrocortisone eye drops was started leading to an immediate reduction of the itching. In both cases an IgE-mediated mechanism is less likely because of the monolateral eye involvement, the complete absence of nasal symptoms, the lack of correlation between symptoms and any pollen season, and the negative prick skin test in one of the two siblings. Both cases suggest that unilateral VKC may occur even in the limbal form and that genetic mechanisms may contribute to the inflammatory reaction in VKC. This report highlights the need for further studies to explain the occurrence of unilateral VKC cases and reminds clinicians to consider the possibility of unilateral limbal VKC in pediatric patients.
PubMed: 37849497
DOI: 10.3389/fped.2023.1237760 -
Frontiers in Pharmacology 2023Allergic conjunctivitis (AC) is a common ophthalmologic disorder that causes symptoms that often reduces a patient's quality of life (QOL). We investigated the effects...
Allergic conjunctivitis (AC) is a common ophthalmologic disorder that causes symptoms that often reduces a patient's quality of life (QOL). We investigated the effects of the eicosapentaenoic acid metabolite (±)5(6)-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid ((±)5(6)-DiHETE) on AC using a mouse model. BALB/c mice were sensitized with two injections of short ragweed pollen in alum, challenged fifth with pollen in eyedrops. The clinical signs and tear volume were evaluated at 15 min after the final challenge. Histamine-induced ocular inflammation model was prepared by instilling histamine onto the surface of the eye. Fifteen minutes after histamine application, tear volume was measured using the Schirmer tear test. Miles assay was performed to investigate vascular permeability. To cause scratching behavior 10 μg of serotonin was injected in the cheek. Repeated topical application of pollen induced conjunctivitis, accompanied by eyelid edema and tearing in mice. Pollen application typically degranulates mast cells and recruits eosinophils to the conjunctiva. Intraperitoneal administration of 300 μg/kg of (±)5(6)-DiHETE significantly inhibited pollen-induced symptoms. The administration of (±)5(6)-DiHETE also attenuated mast cell degranulation and eosinophil infiltration into the conjunctiva. To assess the effects of (±)5(6)-DiHETE on the downstream pathway of mast cell activation in AC, we used a histamine-induced ocular inflammation model. Topical application of 4 μg/eye histamine caused eyelid edema and tearing and increased vascular permeability, as indicated by Evans blue dye extravasation. Intraperitoneal administration of 300 μg/kg or topical administration of 1 μg/eye (±)5(6)-DiHETE inhibited histamine-induced manifestations. Finally, we assessed the effects of (±)5(6)-DiHETE on itching. An intradermal injection of 10 μg serotonin in the cheek caused scratching behavior in mice. Intraperitoneal administration of 300 μg/kg (±)5(6)-DiHETE significantly inhibited serotonin-induced scratching. Thus, (±)5(6)-DiHETE treatment broadly suppressed AC pathology and could be a novel treatment option for AC.
PubMed: 37822881
DOI: 10.3389/fphar.2023.1217397 -
JCI Insight Nov 2023The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest...
The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest symptoms within minutes after pollen exposure, the mechanisms of the rapid transport of the allergens remain unclear. In the present study, we found that the instillation of pollen shells rapidly induces a large number of goblet cell-associated antigen passages (GAPs) in the conjunctiva. Antigen acquisition by stromal cells, including macrophages and CD11b+ dendritic cells, correlated with surface GAP formation. Furthermore, a substantial amount of antigen was transported to the stroma during the first 10 minutes of pollen exposure, which was sufficient for the full induction of an allergic conjunctivitis mouse model. This inducible, rapid GAP formation and antigen acquisition were suppressed by topical lidocaine or trigeminal nerve ablation, indicating that the sensory nervous system plays an essential role. Interestingly, pollen shell-stimulated GAP formation was not suppressed by topical atropine, suggesting that the conjunctival GAPs and intestinal GAPs are differentially regulated. These results identify pollen shell-induced GAP as a therapeutic target for allergic conjunctivitis.
Topics: Animals; Mice; Humans; Conjunctivitis, Allergic; Goblet Cells; Allergens; Pollen; Conjunctiva
PubMed: 37819721
DOI: 10.1172/jci.insight.168596 -
Stem Cell Research & Therapy Oct 2023T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due...
BACKGROUND
T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC).
METHODS
A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 10 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells.
RESULTS
Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice.
CONCLUSIONS
Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.
Topics: Humans; Animals; Mice; Conjunctivitis, Allergic; Conjunctiva; Cytokines; Disease Models, Animal; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 37784129
DOI: 10.1186/s13287-023-03484-4 -
The Journal of Allergy and Clinical... May 2023We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial...
BACKGROUND
We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial (trial no. 206-2-1) that covered 5 pollen dispersal seasons from 2015 to 2019.
OBJECTIVE
Our aim was to perform analysis of the 206-2-1 trial data to evaluate the efficacy of JC pollen SLIT tablets for patients with rhinitis induced by pollen from Japanese cypress (JCY), a related Cupressaceae species that has a pollen dispersal season overlapping with that of JC.
METHODS
Data were analyzed for 240 patients who received placebo during the first pollen dispersal season in 2015, were then rerandomized to receive JC SLIT tablets (the PA group) or placebo (the PP group) for 18 months (the 2016 and 2017 dispersal seasons), and were observed untreated for 2 years (the 2018 and 2019 dispersal seasons). The PA and PP groups were assigned to "high" and "low" subgroups if their rhinitis symptoms were exacerbated/did not change or decreased, respectively, during the peak JCY pollen dispersal period in 2015. The mean total nasal symptom and medication scores and other outcomes were compared for the high-PP, high-PA, low-PP, and low-PA groups during the 2016 to 2019 peak JCY pollen dispersal periods.
RESULTS
The mean total nasal symptom and medication scores were significantly lower for the high-PA and low-PA groups than for the corresponding PP groups over the 4 years of treatment and observation. JCY pollen-specific IgE levels increased in both PA groups.
CONCLUSION
JC pollen SLIT tablets effectively suppressed JCY pollinosis symptoms, supporting the clinical relevance of immunologic cross-reactivity between JC and JCY allergens.
PubMed: 37780797
DOI: 10.1016/j.jacig.2022.10.006 -
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 -
Frontiers in Public Health 2023Asthma is a multifactorial chronic disease, whose most frequent etiology is allergy, especially to . In French Guiana, the childhood prevalence of Blomia T sensitization...
BACKGROUND
Asthma is a multifactorial chronic disease, whose most frequent etiology is allergy, especially to . In French Guiana, the childhood prevalence of Blomia T sensitization is unkwown. The aim of this study was to determine the proportion of sensitization to Blomia T and other mites in asthmatic children, and to describe the characteristics of childhood asthma in French Guiana.
METHODS
A retrospective cohort study focused on children from 0 to 18 years of age, followed for asthma at the Department of Pediatrics of the Cayenne Hospital Center in French Guiana. All asthmatic children followed by the same paediatric allergist were systematically skin-tested with Bt total extract, and Bt-specific IgE tests were additionally performed to confirm specific sensitization. All follow-up variables were collected from medical records. The outcome was sensitization to and other allergens, and the explanatory variables were those of asthma follow-up. Patients were categorized into sensitization yes/no. Logistic regression analysis was used to assess the relationship between follow-up variables and the outcome.
RESULTS
302 patients were followed: 177 cases of allergic rhinitis, 135 allergic conjunctivitis, 105 atopic dermatitis, 153 food allergy, and 14 cases of drug allergy. Poly-allergy (respiratory, food, skin, and medicinal) was present in 239 children. There were 158 children followed for asthma, of whom 103 (65%) were sensitized to . The median age of the asthmatic children sensitized to was 7 years, and 3 years for those who were not sensitized ( < 0.001). Among the girls ( = 58), 67% were sensitized to ; 97 (92%) asthmatic children co-sensitized to , and . Multivariate analysis showed that the childhood asthma in French Guiana is characterized by a median age of 7 years ( < 0.001), a high prevalence of ( < 0.001), co-sensitization to other mites (p < 0.001), and a high prevalence of co-sensitization to cockroaches ( = 0.006). The area under the ROC curve was close to 0.9, confirming the quality of our model.
CONCLUSION
In French Guiana, asthma is characterized by a high prevalence of Blomia tropicalis sensitization.
PubMed: 37744508
DOI: 10.3389/fpubh.2023.1198937 -
Frontiers in Immunology 2023The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only... (Review)
Review
The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.
Topics: Humans; Food Hypersensitivity; Anaphylaxis; Immune Tolerance; Desensitization, Immunologic; Immunity
PubMed: 37744376
DOI: 10.3389/fimmu.2023.1229667 -
Journal of Investigational Allergology... Sep 2023Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free,...
Bilastine 0.6% preservative-free eye drops, an effective once-daily treatment to reduce signs and symptoms of allergic conjunctivitis: A pooled analysis of two randomized clinical trials.
BACKGROUND AND OBJECTIVE
Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free, bilastine 0.6% eye drop formulation for the treatment of allergic conjunctivitis.
METHODS
Two double-masked, vehicle controlled, clinical studies (a Phase 2 Dose Ranging Study and a Phase 3 Efficacy Study) were conducted to assess the efficacy of bilastine ophthalmic solution for the treatment of signs and symptoms of allergic conjunctivitis. Both studies used the Ora-CAC® Conjunctival Allergen Challenge (CAC) Model to allow observations of allergic responses under controlled conditions. Each study was analyzed separately and then combined to create an integrated dataset.
RESULTS
Efficacy was achieved for the primary efficacy endpoint of ocular itching for three bilastine concentrations (0.2%, 0.4%, and 0.6%) at 15 minutes and 8 hours post-instillation and bilastine 0.6% ophthalmic solution was also efficacious at 16 hours post-instillation. Bilastine 0.6% ophthalmic solution demonstrated non-inferiority to ketotifen 0.025% at the onset of action. From the integrated data set, differences between vehicle and bilastine 0.6% were significant at all time points both at onset (15 minutes) and at a prolonged duration (16 hours) after instillation.
CONCLUSION
This multi-trial assessment suggests that bilastine 0.6% ophthalmic solution is efficacious for the treatment of the signs and symptoms of allergic conjunctivitis, with a rapid and prolonged duration of action, and has a favorable safety profile. The added convenience of a once-a-day dosing regimen may contribute to patient adherence and improve their quality of life.
PubMed: 37732873
DOI: 10.18176/jiaci.0940