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1.
J Agric Food Chem ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374318

RESUMO

There have been clinical reports of allergies to dragon fruits. However, little is known about the allergens that trigger these reactions. This study aimed to investigate novel allergens in dragon fruits. The peptide mass fingerprints of two purified natural allergens were identified by LC-MS/MS with chymotrypsin proteolysis. The complete amino acid sequences of the allergens were deduced from cDNA amplicon sequences. The coding sequences of two allergens were inserted in the expression vector pColdI, and recombinant allergens were produced in Escherichia coli. Circular dichroism was performed to analyze the secondary structures of natural and recombinant allergens. Our results identified two novel allergens as Kunitz-type protease inhibitors. Recombinant allergens exhibited well-folded structures, predominantly composed of ß-sheets, similar to their natural counterparts. IgE reactivity analysis with sera from ten patients primarily sensitized to dragon fruit indicated that Kunitz-type protease inhibitors are major allergens in dragon fruits. These results improve our understanding of allergen sources and provide important insights into the allergenicity of proteins from different species.

2.
Ann Med ; 56(1): 2411018, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39364704

RESUMO

OBJECTIVES: Dupilumab, an anti-IL-4 receptor monoclonal antibody (mAb), was recently approved for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). The main objective of this study was to assess whether previous exposure to biological treatment affected the clinical outcomes in CRSwNP and asthma patients, treated with dupilumab over time. A collateral secondary objective was to analyse the effects over time of dupilumab in patients with and without aeroallergen sensitization. METHODS: Single-centre retrospective observational study on severe CRSwNP patients treated with dupilumab. Nasal polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), aeroallergen sensitization, total serum IgE levels, and blood eosinophil counts were assessed at baseline and after 4, 6 and 12 months. RESULTS: 42 patients were included, 40 (95.2%) had asthma. Twenty-one (50%) patients received dupilumab without prior biological treatment (Group A: naive) and 50% switched to dupilumab from previous biological treatment (Group B: pre-treated). NPS, VAS symptoms, SNOT-22 improved significantly after 12 months treatment in both groups of patients (p < 0.001). After 12 months, VAS overall symptom score showed a significant reduction from 6 (IQR, 4.6-8.6) and 6 (IQR, 3.8-7.1) for Group A and Group B patients respectively, to 1.2 (IQR, 0.8-2.7) and 1.2 (IQR, 0.2-2.5); NPS from 6 (IQR, 4.0-7.0) and 5 (IQR, 3.5-6.0), respectively, to 1 (IQR, 0.0-2.0) and 0 (IQR, 0.0-3.0) and SNOT-22 from 64 (IQR, 56-78) and 71 (IQR, 47.5-76.0) respectively, to 5.5 (IQR, 4-21) and 6 (IQR, 4-15). IgE reduced from 57 to 22.1 and from 46.9 to 30.2 in Group A and Group B respectively (p < 0.001). CONCLUSIONS: Dupilumab improves symptom severity, polyp size, and health-related quality of life, regardless of the presence or absence of comorbid aeroallergen sensitization and previous administration of biologic therapy.


Dupilumab proved to be effective in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).We observed that dupilumab for CRSwNP leads to a very rapid improvement in polyps, symptoms, and quality of life, regardless of previous biologic treatment status and presence or absence of allergic rhinitis.VAS, SNOT-22 and NPS may be established as outcome markers in everyday clinical practice during dupilumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados , Asma , Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Pólipos Nasais/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Sinusite/tratamento farmacológico , Sinusite/complicações , Sinusite/imunologia , Asma/tratamento farmacológico , Asma/complicações , Asma/imunologia , Rinite/tratamento farmacológico , Rinite/imunologia , Rinite/complicações , Doença Crônica , Adulto , Resultado do Tratamento , Idoso , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Rinossinusite
3.
Clin Exp Allergy ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363801

RESUMO

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

4.
Front Immunol ; 15: 1452410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351215

RESUMO

The prevalence of allergic rhinitis (AR) in children is steadily increasing, and its onset is closely associated with genetic factors, living environment, and exposure to allergens. In recent years, an increasing number of diagnostic methods have been employed to assist in diagnosing AR. In addition to pharmaceutical treatments, personalized approaches such as environmental control and allergen-specific immunotherapy are gradually gaining popularity. In this article, we reviewed recent research on the etiology, diagnostic classification, treatment methods, and health management of AR in children. These insights will benefit the implementation of personalized diagnosis and treatment for children with AR, promoting health management strategies that improve symptoms and quality of life.


Assuntos
Rinite Alérgica , Humanos , Rinite Alérgica/terapia , Rinite Alérgica/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Criança , Dessensibilização Imunológica/métodos , Alérgenos/imunologia , Qualidade de Vida , Medicina de Precisão
5.
Mol Immunol ; 175: 121-131, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357098

RESUMO

BACKGROUND: The house-dust mite Dermatophagoides pteronyssinus is a key trigger of allergic asthma. Therefore, it is essential to develop new vaccines that can alter inflammatory processes and airway remodeling. The goal of this study was to test the hypoallergenic and immunogenic characteristics of the hypoallergen rDer p 2231 in a murine model of chronic asthma induced by D. pteronyssinus. METHODS: For this, we measured the levels of IgE, IgG1, IgG2a, and cytokines produced by mice receiving the rDer p 2231 protein. Histopathological parameters of the chronic inflammatory response were also investigated by assessing inflammation and airway remodeling. RESULTS: rDer p 2231 given as a therapeutic vaccine, led to a reduction in the production of IgE, eosinophils, and neutrophils, a lower activity of eosinophilic peroxidase in the airways, and an increase in the production of IgG1 and IgG2a antibodies. IgG antibodies blocked IgE binding to parental allergens in sera from atopic patients. Splenocytes, BALF, and lung from mice treated with rDer p 2231 secreted higher levels of Th1 and regulatory cytokines, as well as reduced levels of Th2 cytokines. Histopathological investigation of the lower airways demonstrated reductions in the thickness of the bronchiolar smooth muscle layer, in the subepithelial fibrosis, and in the goblet cells hyperplasia. CONCLUSIONS: Our preclinical studies suggest that rDer p 2231 is a promising candidate for the treatment of D. pteronyssinus allergy, as the hypoallergen has demonstrated the ability to reduce IgE production, induce specific blocking antibodies, restore and balance Th1/Th2 immune responses, and significantly reduce airway remodeling factors. However, additional clinical studies are needed to more accurately assess the efficacy and safety of rDer p 2231 as a vaccine against D. pteronyssinus-induced allergy.

6.
BMC Biotechnol ; 24(1): 72, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367362

RESUMO

BACKGROUND: Timothy grass (Phleum pratense) is a significant source of allergens, and recombinant allergens are increasingly used for diagnostic purposes. However, the performance of different recombinant allergen production systems in diagnostic assays needs further investigation to optimize their use in clinical settings. OBJECTIVE: The main objective of this study was to analyze and compare the diagnostic performance of recombinant timothy grass allergens produced in E. coli and N. benthamiana using a custom-made microarray chip. METHODS: Recombinant timothy grass allergens Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 11, and Phl p 12 were produced in E. coli and/or N. benthamiana. A total of 113 patient serum samples were tested to evaluate the diagnostic sensitivity, specificity, inter-assay variability, and correlation of allergen-specific IgE detection compared to commercial multiplex tests (ALEX and ISAC). Additionally, the prevalence of sIgE to these allergens was assessed. RESULTS: Phl p 1, Phl p 2, Phl p 5, Phl p 6 and Phl p 11 showed high or very high positive correlation in immunoreactivity with other commercial multiplex tests. Notably, Phl p 11 fused with maltose-binding protein (MBP) demonstrated high diagnostic specificity and sensitivity, with a 0.3 arbitrary cut-off value. However, a high intra-assay variation was observed. The study also assessed specific IgE prevalence to timothy grass allergens within the tested patient cohort. CONCLUSIONS: Recombinant allergens from both E. coli and N. benthamiana demonstrated strong diagnostic potential on the microarray platform, with Phl p 11 (MBP-fused) showing particularly high performance. High intra-assay variation highlights the need for further optimization in allergen formulation and microarray storage conditions. These results highlight the potential of recombinant allergens for diagnostic applications, despite challenges with allergen stability in microarray formats. Specific IgE prevalence to timothy allergens revealed a sensitization profile consistent with findings from multiple studies.


Assuntos
Alérgenos , Escherichia coli , Imunoglobulina E , Phleum , Proteínas Recombinantes , Phleum/imunologia , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Alérgenos/imunologia , Alérgenos/genética , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Sensibilidade e Especificidade , Proteínas de Plantas/imunologia , Proteínas de Plantas/genética , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Análise Serial de Proteínas/métodos
7.
J Clin Med ; 13(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39274456

RESUMO

Background: Urticaria is a common disease with a marked influence on quality of life. The key cell involved is the mast cell, which can be activated by a vast variety of stimuli, and the major mediator is histamine. Allergic urticaria is a disorder with a large variety of causes: food, drugs, insect venom, skin contact with allergens, and physical exercise. Buckwheat consumption has increased in European countries and the USA because it is gluten-free. It can trigger anaphylactic shock if ingested, inhaled, or handled with the hands. Five common buckwheat allergens named Fag e1 to 5 (Fag e1, 2, and 3 are considered the major allergens) and two tartary buckwheat allergens named Fag t1 and Fag t2 have been described. Method: We present the case of a patient who experienced two anaphylactic shocks and in whom the etiological factor was buckwheat. The patient presented to the Allergology department for the evaluation of two episodes of severe allergic reactions that required emergency therapy, episodes that involved the loss of consciousness and were of major severity. At each anaphylactic shock, an ambulance was requested, and emergency therapy was administered, leading to the patient's recovery within a few hours. Diagnosis: Since each episode occurred a few minutes after eating, the diagnosis was established based on a detailed anamnesis and prick skin tests, followed by specific IgE dosages. Other foods consumed by the patient, assessed by prick skin testing and specific IgE dosages of suspected foods, were excluded as the etiological cause. Increased levels of buckwheat-specific immunoglobulin E were highlighted, thus identifying the etiological agent. The treatment of anaphylactic shock was performed urgently by the ambulance crew with adrenaline, infusion solutions, cortisone preparations, and antihistamines. Result: Following the treatment that was initiated, there was a partial remission of the lesions after a few hours. Conclusions: Buckwheat allergy is rare, but it produces symptoms that affect the skin, gastrointestinal tract, and respiratory tract, as well as anaphylaxis. In a professional environment, it can trigger allergic rhinitis, asthma, and hives. Although buckwheat allergens have been described, their clinical relevance has only been studied in a small number cases. In current practice, the only commercially available allergen is Beech e2 per the ImmunoCAP ISAC microarray. Diagnosis can be difficult in clinical practice. This reported case suggests the need for a thorough anamnesis, since buckwheat is consumed as a hidden allergen, and in Europe, it is not necessary to label foods containing this allergen.

8.
Parasites Hosts Dis ; 62(3): 351-364, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39218634

RESUMO

The gut microbiome plays an essential role in host immune responses, including allergic reactions. However, commensal gut microbiota is extremely sensitive to antibiotics and excessive usage can cause microbial dysbiosis. Herein, we investigated how changes in the gut microbiome induced by ampicillin affected the production of IgG1 and IgG2a antibodies in mice subsequently exposed to Anisakis pegreffii antigens. Ampicillin treatment caused a notable change in the gut microbiome as shown by changes in both alpha and beta diversity indexes. In a 1-dimensional immunoblot using Anisakis-specific anti-mouse IgG1, a 56-kDa band corresponding to an unnamed Anisakis protein was detected using mass spectrometry analysis only in ampicillin-treated mice. In the Anisakis-specific anti-mouse IgG2a-probed immunoblot, a 70-kDa band corresponding to heat shock protein 70 (HSP70) was only detected in ampicillin-treated and Anisakis-immunized mice. A 2-dimensional immunoblot against Anisakis extract with immunized mouse sera demonstrated altered spot patterns in both groups. Our results showed that ampicillin treatment altered the gut microbiome composition in mice, changing the immunization response to antigens from A. pegreffii. This research could serve as a basis for developing vaccines or allergy immunotherapies against parasitic infections.


Assuntos
Ampicilina , Anisakis , Microbioma Gastrointestinal , Imunoglobulina G , Animais , Anisakis/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Ampicilina/farmacologia , Camundongos , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Antígenos de Helmintos/imunologia , Feminino , Anisaquíase/imunologia , Anisaquíase/parasitologia , Anticorpos Anti-Helmínticos/imunologia , Imunização
9.
Molecules ; 29(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39274971

RESUMO

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies.


Assuntos
Hipersensibilidade Alimentar , Nanopartículas , Polietilenoglicóis , Animais , Nanopartículas/química , Polietilenoglicóis/química , Camundongos , Hipersensibilidade Alimentar/terapia , Hipersensibilidade Alimentar/imunologia , Imunoterapia/métodos , Muramidase/química , Feminino , Pele/efeitos dos fármacos , Pele/metabolismo , Imunoglobulina G/sangue , Administração Cutânea , Camundongos Endogâmicos BALB C , Poliglactina 910/química , Portadores de Fármacos/química , Poliésteres
10.
Nutrients ; 16(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39275185

RESUMO

BACKGROUND: Cross-reactivity between nonspecific lipid transfer proteins could cause anaphylaxis, further influencing food avoidance and nutrient deficiencies. The one affecting olive pollen (Ole e 7) and peach (Pru p 3) may underlie a variety of pollen-food syndromes, though a deep molecular analysis is necessary. METHODS: Three Ole e 7-monosensitised patients (MON_OLE), three Pru p 3-monosensitised patients (MON_PRU) and three bisensitised patients (BI) were selected. For epitope mapping, both digested proteins were incubated with patient sera, and the captured IgE-bound peptides were characterised by LC-MS. RESULTS: The analysis revealed two Ole e 7 epitopes and the three Pru p 3 epitopes previously described. Interestingly, the "KSALALVGNKV" Ole e 7 peptide was recognised by MON_OLE, BI and MON_PRU patients. Conversely, all patients recognised the "ISASTNCATVK" Pru p 3 peptide. Although complete sequence alignment between both proteins revealed 32.6% identity, local alignment considering seven residue fragments showed 50 and 57% identity when comparing "ISASTNCATVK" with Ole e 7 and "KSALALVGNKV" with Pru p 3. CONCLUSIONS: This study mapped sIgE-Ole e 7-binding epitopes, paving the way for more precise diagnostic tools. Assuming non-significant sequence similarity, structural homology and shared key residues may underlie the potential cross-reactivity between Ole e 7 and Pru p 3 nsLTPs.


Assuntos
Antígenos de Plantas , Reações Cruzadas , Hipersensibilidade Alimentar , Imunoglobulina E , Olea , Proteínas de Plantas , Pólen , Prunus persica , Humanos , Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/imunologia , Pólen/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Olea/imunologia , Proteínas de Plantas/imunologia , Feminino , Masculino , Prunus persica/imunologia , Mapeamento de Epitopos , Adulto , Rinite Alérgica Sazonal/imunologia , Sequência de Aminoácidos , Epitopos/imunologia , Alérgenos/imunologia , Pessoa de Meia-Idade , Proteínas de Transporte/imunologia
11.
Arch Dermatol Res ; 316(9): 620, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276233

RESUMO

Asthma is a respiratory disorder caused by airway inflammation which may worsen after allergen exposure. Recent cohort studies demonstrate a positive association between skin cancer and asthma or hay fever (allergy to outdoor allergens such as pollen). Nationally-representative data for adults in the United States remains limited. We aimed to characterize skin cancer prevalence among individuals in the United States who have asthma or hay fever. To achieve this aim, we extracted nationwide cross-sectional data from 16,277 adult participants (total survey-weighted sample = 174,765,931) of the Third National Health and Nutrition Examination Survey from 1988 to 1994. This study uses survey-weighted regression to compare the nationwide prevalence of skin cancer among participants with or without a history of asthma or hay fever. Sensitivity analysis examined the influence of sex, 25-hydroxyvitamin D, chronic bronchitis or emphysema, geographical region, urban proximity, and oral glucocorticoid use. Of the included participants, the age-adjusted prevalence of skin cancer was 7.2%, similar to national estimates. Skin cancer prevalence was higher among participants who had asthma with hay fever (adjusted prevalence ratio, 1.79; 95% confidence interval, 1.16, 2.76), but not among participants with asthma only or hay fever only. Similarly, skin cancer prevalence was higher for those with asthma and positive pollen allergen skin prick testing (SPT), but not for those with hay fever and positive pollen SPT. No association was noted between skin cancer and wheezing triggered by pollen. Hay fever or immunoglobulin-E sensitization to pollen may increase skin cancer prevalence among individuals with a history of asthma.


Assuntos
Asma , Inquéritos Nutricionais , Rinite Alérgica Sazonal , Neoplasias Cutâneas , Humanos , Estudos Transversais , Masculino , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/diagnóstico , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/diagnóstico , Prevalência , Asma/epidemiologia , Asma/imunologia , Asma/diagnóstico , Alérgenos/imunologia , Alérgenos/efeitos adversos , Testes Cutâneos , Idoso , Adulto Jovem , Pólen/imunologia , Pólen/efeitos adversos , Fatores de Risco
12.
Food Chem ; 463(Pt 2): 141221, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39276555

RESUMO

Allergy to novel food proteins, due to diverse ingredients and innovative food processing technologies employed to achieve desired functional properties, is a major safety concern. Current allergy testing methods (ELISA and mass spectrometry) depend on high-quality protein extracts, meaning existing methods are often tailored to specific matrices. Therefore, a more efficient and general protein extraction method is desirable for comprehensive allergy risk assessment. Here, we developed a highly efficient and reproducible protein extraction method which achieved at least 80 % efficiency across several food matrices. Proteomics analysis of a plant-based meat using our optimized extraction method showed that higher extraction efficiency improved reproducibility of identified proteins. Moreover, higher protein extraction efficiency resulted in increased abundances of individual allergenic proteins. This underscores the relevance of our method for more accurate measurements of allergenic protein concentrations in allergy risk assessments.

13.
Allergol Immunopathol (Madr) ; 52(5): 89-93, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39278857

RESUMO

In this cross-sectional, descriptive, and observational study conducted at Fundación Valle del Lili in Colombia, the clinical and sociodemographic characteristics of anaphylaxis were investigated in a cohort of 80 patients who sought medical care between January 2021 and December 2022. With a median age of 16 years and a notable prevalence among individuals aged below 18 years, the study revealed that 63.8% of patients had concomitant allergic diseases. Medications emerged as the primary triggers for anaphylaxis, followed by food. The mucocutaneous system was predominantly affected in 55% of cases, with respiratory involvement observed in 37.5%. Alarmingly, anaphylactic shock occurred in 17.5%, and 7.5% experienced biphasic anaphylaxis. Intramuscular adrenaline was administered in 88.8% of cases, with 75% of patients not receiving an allergy consultation upon discharge, and 52.5% lacking follow-up for allergy care. Considering that in Colombia epidemiological data on the clinical and sociodemographic aspects of anaphylaxis remain largely unknown, this study documents the features of anaphylaxis in both adult and pediatric populations and highlights the urgent need for improved awareness, timely evaluation by allergists, and comprehensive follow-up care for individuals experiencing anaphylaxis.


Assuntos
Anafilaxia , Humanos , Anafilaxia/epidemiologia , Colômbia/epidemiologia , Masculino , Feminino , Adolescente , Adulto , Estudos Transversais , Adulto Jovem , Criança , Pessoa de Meia-Idade , Pré-Escolar , Prevalência , Epinefrina/administração & dosagem , Hipersensibilidade Alimentar/epidemiologia , Lactente , Idoso
14.
Front Immunol ; 15: 1367971, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229267

RESUMO

Introduction: Equine asthma (EA) is a common disease of adult horses with chronic respiratory pathology and common neutrophilic airway inflammation. It presents with hyperreactivity to hay dust components such as molds, and underlying dysregulated T cell responses have been suggested. Thus far, T cells have been analysed in EA with conflicting results and the antigen reactivity of T cells has not been demonstrated. Serological and epidemiological data point to the relevance of Aspergillus fumigatus as an antigen source in EA. Here, we aimed to identify and characterise Aspergillus antigen-reactive T cells in EA. Methods: Cryopreserved bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) from healthy horses (HE, n=9) and those with mild-moderate (MEA, n=3) or severe asthma (SEA, n=8) were stimulated in vitro with the recombinant A. fumigatus antigens Asp f 1, or Asp f 7 combined with Asp f 8, to assess antigen reactivity, and with phorbol-12-myristat-13-acetate and ionomycin (P/i) to assess overall T cell reactivity. Stimulated cells were analysed by flow cytometry for CD4, CD8, IL-17, IL-4, and IFN-γ. Cytokine expression in all lymphocytes, and in CD4+ or CD8+ T cells, was quantified and compared between the groups. In BAL fluid (BALF), soluble cytokines and chemokines were quantified by bead-based assays. Results: Antigen restimulation of BALC with Asp f 1 or Asp f 7/8 provoked higher frequencies of IL-17+ lymphocytes, CD4+IL-17+ Th17 cells, and CD4+IL-4+ Th2 cells in SEA than in HE, whereas MEA and HE were similar. Antigen stimulation of PBMC did not result in group differences. P/i stimulation of BALC resulted in increased IL-17+ lymphocyte and CD4+IL-17+ Th17 cell frequencies in MEA compared with HE but the limited number of horses with MEA must be considered. P/i-stimulated PBMC from MEA or SEA contained more IL-17+ lymphocytes compared with HE. Cytokines were hardly detected in BALF and similar between the groups but CCL2 and CCL5 concentrations were increased in BALF from SEA or MEA, respectively, compared with HE. Conclusion: Horses with SEA have increased Aspergillus antigen-reactive Th17 cells in their airways, emphasising local T cell responses to this mold, which were quantified in EA for the first time here.


Assuntos
Antígenos de Fungos , Aspergillus fumigatus , Asma , Líquido da Lavagem Broncoalveolar , Citocinas , Doenças dos Cavalos , Células Th17 , Animais , Células Th17/imunologia , Asma/imunologia , Aspergillus fumigatus/imunologia , Cavalos/imunologia , Antígenos de Fungos/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/microbiologia , Citocinas/metabolismo , Masculino , Feminino
15.
J Allergy Clin Immunol Glob ; 3(4): 100310, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39234416

RESUMO

Background: Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia. Objective: In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge. Methods: A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11). Allergen and saline control intradermal challenges were conducted before and after treatment, with skin biopsy samples collected 24 hours after challenge. Early and late cutaneous responses were measured by skin wheal size. Levels of eosinophils and IL-5 receptor-α-bearing cells, including eosinophil progenitor (EoP) cells, basophils, and mast cells, in papillary dermis were measured by immunofluorescence microscopy, and levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood were measured by flow cytometry. Outcomes were compared between the placebo and benralizumab treatment groups by using the Mann-Whitney U test. Results: Benralizumab reduced eosinophil counts in the blood (P < .0001) and allergen-challenged skin, as measured by hematoxylin and eosin staining and eosinophil cationic protein antibody concentration (P < .05). Benralizumab lowered the levels of EoP cells, mast cells, and basophils in the skin, as well as the levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood (all P < .05). There was a trend toward improvement in the early cutaneous response (P = .095) but no effect on the late cutaneous response. Conclusion: In patients with moderate-to-severe AD, benralizumab treatment significantly inhibited accumulation of eosinophils and other IL-5 receptor-α-expressing cells in the papillary dermis after intradermal allergen challenge. Targeting IL-5 receptor-α-positive cells did not modulate the size of the allergen-induced skin wheal (ClincialTrials.gov identifier NCT03563066).

16.
Artigo em Inglês | MEDLINE | ID: mdl-39219549

RESUMO

Summary: Background. Allergen immunotherapy (AIT) is the only disease-modifying treatment in allergy. Its efficacy has been demonstrated in the treatment of Local Allergic Rhinitis (LAR) in adults. This study intends to evaluate the effectiveness of AIT in specific nasal reactivity of paediatric patients with LAR. Methods. Patients diagnosed with LAR to Dermatophagoides pteronyssinus (Dp) were submitted to subcutaneous AIT (SCIT) (depigmented-polymerized Dp allergen extracts) for 3 years. Nasal allergen challenge (NACs) with Dp extract were performed before and 3 years after AIT. NAC response was assessed with peak nasal inspiratory flow (PNIF) and symptom score of Lebel. NACs were considered positive when there was a flow decrease of ≥ 20% in PNIF and a score of symptoms ≥ 3 points. Demographic data and NAC results were analysed. Results. We included 32 paediatric patients (mean age 9.9±3.08 years, 18 female) and 10 adult patients, (mean age 30.4±12.2 years, 7 female). The symptom score obtained at the 1st minute, 5th minute, 15th minute and 30th minute in response to NAC, were reduced after AIT. The nasal inspiratory flow decrease induced by NAC was also reduced after AIT.  This reduction in nasal reactivity was observed in paediatric and in adult patients, both with statistical significance. Conclusions. AIT induced a decrease in Dp-nasal specific reactivity in children with LAR. This decline of nasal response to allergen exposure, after AIT treatment, emphasis the interest of this therapeutic approach in LAR, even in paediatric patients.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39221486

RESUMO

Summary: Background. Current recommendations for infant weaning suggest introducing common food allergens by the age of 12 months. While homemade meals are advisable, there is a notable demand for commercially available complementary foods (CACF). Furthermore, emerging evidence suggests a potential link between the consumption of ultra-processed products and the incidence of allergic diseases. This study aimed to examine the presence of the fourteen main food allergens in CACF ingredients through label analysis and evaluate their extent of processing. Methods. Between January and February 2024, labels of all CACF found in infant feeding sections of 10 Portuguese grocery retailers were analyzed. CACF were categorized based on the NOVA food classification system's processing levels. Milk formulas, products for children over 15 months, and those for children with food allergies or intolerances were excluded Results. Of the 492 products analysed, 132 contained wheat and 112 contained milk. 16 products included fish and 6 contained egg. Soy was listed as an ingredient in 11 products, mainly as soy lecithin. Only 2 product contained nuts, and 1 product contained peanuts. None of the products contained the remaining six allergens. The majority of milk- and wheat-containing products were classified as ultra-processed and contained added sugars and/or sweeteners. Conclusions. Despite the current guidelines, commercial baby foods often lack major allergens, namely nuts and peanuts, eggs, and shellfish. Our results underscore the need for healthy, age-appropriate, minimally processed products that incorporate rather than exclude major food allergens.

18.
Artigo em Inglês | MEDLINE | ID: mdl-39222196

RESUMO

PURPOSE OF REVIEW: While there are compelling arguments for developing subcutaneous allergen-specific immunotherapy for alleviation of food allergies, there is a limited number of studies in the public domain. The review seeks to present the approaches taken, to explain the paucity of studies, and to identify new roads for development. RECENT FINDINGS: A literature search revealed clinical trials of immunotherapy of food allergies to fish and peanut, but studies had limited patient numbers, short treatment courses and follow-up periods. Indications, but no clearcut effects, were seen with both classical allergen extracts and hypo-allergenic preparations. A special case is the influence on cross-reactive food allergies, when subcutaneously administered birch-pollen extracts are used for treatment of birch pollen hayfever and/or asthma. Again indications, but no convincing efficacy has been registered. Newer developments include recombinant hypoallergens and DNA-technologies. Subcutaneous immunotherapy for food allergies has not matured to provide clinically relevant treatment opportunities.

19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 565-574, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39223021

RESUMO

Hymenopteran insect stings are a risk factor that cannot be ignored for the people allergic to hymenopteran venoms.In China,the current diagnostic tools cannot provide accurate information to identify sensitized insects,thus affecting clinical diagnosis and treatment.Honeybee is a common hymenopteran insect.Due to its wide distribution,large number,and complex venom composition,researchers have carried out recombination schemes for the main allergens of honeybee venom,laying a theoretical foundation for the detection of allergens.The development of diagnostic technologies for allergen components can accurately detect bee venom allergens,providing a new set of clinical diagnosis and treatment schemes for the population allergic to bee venom.


Assuntos
Alérgenos , Venenos de Abelha , Venenos de Abelha/imunologia , Alérgenos/análise , Alérgenos/imunologia , Animais , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Abelhas/imunologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-39254378

RESUMO

IL-4 and IL-13 play a critical role in allergic asthma pathogenesis via their common receptor, i.e., IL4Rα. However, the cell-specific role of IL4Rα in mixed allergens (MA)-induced allergic asthma has remained unclear. Therefore, we aimed to identify the cell-specific contribution of IL4Rα signaling in the manifestation of various pathological outcomes in mice with allergic airway disease. We compared MA-induced pathological outcomes between hematopoietic progenitor cells (HPCs)- or non-HPCs-specific IL4Rα-deficient chimera, myeloid cell-specific IL4Rα-deficient (LysMcre+/+/IL4Rαfl/fl), and airway epithelial cell-specific IL4Rα-deficient (CCSP-Cre+ /IL4Rαfl/fl) mice. Chimeric mice with systemic IL4Rα sufficiency displayed hallmark features of allergic asthma, including eosinophilic and lymphocytic infiltration, type 2 (Th2) cytokine/chemokine production, IgE production, and lung pathology. These features were markedly reduced in chimeric mice with systemic IL4Rα deficiency. Non-HPCs-specific IL4Rα-deficient mice displayed typical inflammatory features of allergic asthma but with markedly reduced mucous cell metaplasia (MCM). Deletion of IL4Rα signaling on airway epithelial cells, a subpopulation within the non-HPC lineage, resulted in almost complete absence of MCM. In contrast, all features of allergic asthma except for MCM and mucin production were mitigated in HPCs-specific IL4Rα-deficient chimeric mice. Deleting IL4Rα signaling in myeloid cells, a subpopulation within the HPC lineage, significantly alleviated MA-induced allergic airway inflammatory responses, but similar to the HPCs-specific IL4Rα-deficient chimeric mice, these mice showed significant MCM and mucin production. Our findings demonstrate that the differential allergen responsiveness seen in mice with HPCs-specific and non-HPCs-specific IL4Rα deficiency is predominantly driven by the absence of IL4Rα in myeloid cells and airway epithelial cells, respectively. Our findings also highlight distinct and mutually exclusive roles of IL4Rα signaling in mediating pathological outcomes within the myeloid and airway epithelial cell compartments.

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