Dataset Information

Changes in the Sensitization Pattern to Alternaria alternata Allergens in Patients Treated with Alt a 1 Immunotherapy.

ABSTRACT: Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of immunotherapy with native major allergen Alt a 1 were analyzed by immunoblotting; 98. 4% of the patients recognized Alt a 1. The percentage of recognition for Alt a 3, Alt a 4, and/or Alt a 6, Alt a 7, Alt a 8, Alt a 10 and/or Alt a 15 was 1.6%, 21.9%, 12.5%, 12.5%, and 12.5% respectively. Of the 64 patients, 45 (70.3%) only recognized Alt a 1 among the allergens present in the A. alternata extract. Immunotherapy with Alt a 1 desensitizes treated patients, reducing their symptoms and medication consumption through the elimination of Alt a 1 sensitization, which is no longer present in the immunoblotting of some patients. There may be gender differences in the pattern of sensitization to A. alternata allergens, among others.

SUBMITTER: Rodriguez D

PROVIDER: S-EPMC8618185 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Changes in the Sensitization Pattern to Alternaria alternata Allergens in Patients Treated with Alt a 1 Immunotherapy.

Rodríguez David D Tabar Ana I AI Castillo Miriam M Martínez-Gomariz Montserrat M Dobski Isabel C IC Palacios Ricardo R

Journal of fungi (Basel, Switzerland) 20211116 11

Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of ...[more]

PMID: 34829261

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Project description:BackgroundThe efficacy of allergen-specific subcutaneousimmunotherapy (SCIT) with Alt a 1 of the fungus A. alternata is still unknown. Yet, few studies compare the therapeutic effects and immunological mechanisms of Alt a 1 and A. alternata extracts. We aim to explore and compare the changes in allergic inflammation and immunological mechanisms of Alt a 1 and A. alternata in mice.MethodsFemale BALB/c mice administrated recombinant Alt a 1 (rAlt a 1), native Alt a 1 (nAlt a 1), and A. alternata. Lung histology, airway hyper-reactivity (AHR), bronchoalveolar lavage fluid (BALF) cytokine levels, serum immunoglobulin responses, the expression of Bcl-6, the percentages of T follicular helper cells (Tfh), cytokine-related Tfh subtypes, regulatory B cells (Breg), and IL-10+ Breg cells were detected.ResultsHigh-purity nAlt 1 protein was obtained. SCIT with Alt a 1 and Alternaria decreased airway and lung inflammation, including improvement of lung pathology, lower levels of AHR, reduction of total cell numbers, and IL-4 and IL-13 levels in BALF. Furthermore, Alt a 1-SCIT effectively suppressed the IgE responses, elevated IgG titers, and was superior in decreasing the expression of Bcl-6. Additionally, Alternaria-SCIT significantly decreased the expression of Tfh cells, L-4+ Tfh, and IL-5+ Tfh cells in the spleen, whereas Alt a 1 showed superior therapeutic effects in the lymph node. IL-13+ Tfh cells in these two treatment groups not being significant. IL-17A+ Tfh cells were alleviated most effectively after A. alternata-SCIT in both the spleen and lymph node. Intriguingly, IL-10+ Breg cells decreased remarkably in response to SCIT with rAlt a 1.ConclusionsTreatments with Alt a 1 and A. alternata extracts had beneficial effects on allergic inflammation. Alt a 1-SCIT resulted in prominent improvement in the immunoglobulin responses, Bcl-6, and IL-10+ Breg cells. Alternaria-SCIT was more likely to suppress the expression of Tfh and cytokine-related Tfh subtypes.

Project description:BackgroundPollen released by allergenic members of the botanically unrelated families of Asteraceae and Cupressaceae represent potent elicitors of respiratory allergies in regions where these plants are present. As main allergen sources the Asteraceae species ragweed and mugwort, as well as the Cupressaceae species, cypress, mountain cedar, and Japanese cedar have been identified. The major allergens of all species belong to the pectate lyase enzyme family. Thus, we thought to investigate cross-reactivity pattern as well as sensitization capacities of pectate lyase pollen allergens in cohorts from distinct geographic regions.MethodsThe clinically relevant pectate lyase pollen allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen extracts, and patients' sensitization pattern of cohorts from Austria, Canada, Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments. Moreover, we performed microarray experiments and established a mouse model of sensitization.ResultsIn ELISA and ELISA inhibition experiments specific sensitization pattern were discovered for each geographic region, which reflected the natural allergen exposure of the patients. We found significant cross-reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens, which was however limited between the orders. Animal experiments showed that immunization with Asteraceae allergens mainly induced antibodies reactive within the order, the same was observed for the Cupressaceae allergens. Cross-reactivity between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in general higher immunogenicity.ConclusionWe could cluster pectate lyase allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1, respectively, at which each category has the potential to sensitize predisposed individuals. The sensitization pattern of different cohorts correlated with pollen exposure, which should be considered for future allergy diagnosis and therapy.

Dataset Information

Changes in the Sensitization Pattern to Alternaria alternata Allergens in Patients Treated with Alt a 1 Immunotherapy.

Publications

Changes in the Sensitization Pattern to <i>Alternaria alternata</i> Allergens in Patients Treated with Alt a 1 Immunotherapy.

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