Clinical outcome and component-specific antibody levels in egg allergic children after lightened oral immunotherapy

Objective: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet. Patients and methods: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy. Results: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization. Conclusion: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT (AU)

Snail-induced anaphylaxis in patients with underlying Artemisia vulgaris pollinosis: the role of carbohydrates

Purpose: The importance of carbohydrates in anaphylaxis has been described with some foods. The current work intends to obtain clinical and immunological evidence of the importance of the O-glycans for IgE binding activity in anaphylactic reactions due to Helix aspersa (HA) ingestión and Artemisia vulgaris (AV) exposition. Methods: The studio focused on two cases of IgE-mediated anaphylaxis induced by snail ingestion in patients with underlying rhino-conjunctivitis and asthma due to AV. We performed on both patients: skin prick tests ( SPTs) with HA and AV and with a battery of aeroallergen, controlled nasal challenge and specific IgE to HA and AV, ImmunoCAP ISAC®, and a differential pattern of IgE recognition with SDS-PAGE Immunoblotting (SDSI) when these allergens have suffered an O-deglycosylation procedure. Results: The patients showed positive results in SPTs, nasal challenges, and serum-specific IgE against HA and AV. In patient 1, the SDSI detected several IgE-binding proteins in AV with a molecular mass of 22, 24, and 44 kDa, whereas a band of 12 kDa was detected in HA. On the other hand, patient 2’s serum revealed an IgE-binding zone between 75 and 20 kDa in the AV and a band of 24 kDa in the HA. When glycans were removed, patient 1’s serum only revealed the AV’s 22 and 24 kDa bands, whereas patient 2’s serum did not detect any IgE-reactive protein in the HA. Conclusions: Our data suggest that O-glycosylation can be relevant in patients with anaphylaxis due to snails and allergy to Artemisia vulgaris. This new entity representing cross-reactivity between AV and HA could be named Snail-Artemisia Syndrome (AU)

Exposure to farm environment and its correlations with total IgE, IL-13, and IL-33 serum levels in patients with atopy and asthma

Background: The aim of the study was to evaluate total immunoglobulin E (IgE), IL-13, and IL-33 serum level in people with bronchial asthma and atopy, and in healthy control group depending on their exposure to farm animals currently and in the first year of life. Methods: The study included 174 individuals living in rural areas and in a small town. Standardized questions from the International Study of Asthma and Allergy in Childhood and The European Community Respiratory Health Survey (ECRHS) questionnaires were used to define asthma. Atopic status was verified by skin prick tests. Rural exposure including contact with livestock was verified by adequate questionnaire. Total serum IgE, IL-13, and IL-33 levels were assessed by ELISA (enzyme-linked immunosorbent assay) tests. Results: Participants with atopy and bronchial asthma were characterized by high level of immunoglobulin E. Tendency to lower serum IgE level was observed among people reporting present contact with farm animals. Also, among those having contact with livestock in their first year of life, the analogous tendency was noticed. No difference in serum IL-13 levels in participants with asthma and atopy, and controls was observed, and there was no effect of exposure on farm animals on the concentration of IL-13. The highest IL-33 level was found in the atopic group, and the lowest in the control group. Participants currently exposed to farm animals were predisposed to have lower IL-33 serum level. Conclusion: Exposure of farm animals currently and in first year of life may result in a lower level of total IgE. Correlation between IL-13 and IL-33 serum levels and contact with livestock was not confirmed (AU)

Enfermedad de Kimura en paciente no asiática / Kimura’s disease in a non-asian patient

La enfermedad de Kimura es un trastorno inflamatorio benigno poco frecuente, de etiología desconocida y que afecta principalmente a sujetos de origen asiático. Clínicamente se manifiesta como masas subcutáneas, indoloras, sobre todo en la zona de cabeza y el cuello. Suele acompañarse de linfadenopatías, y aumento de los niveles de eosinófilos e IgE en sangre periférica. Se presenta un caso de enfermedad de Kimura, diagnosticado en una mujer caucásica tras la exéresis-biopsia de una masa mandibular de gran tamaño. Describir esta patología ayudará a incluir la misma en el diagnóstico diferencial de masas, sobre todo a nivel cervico-facial, favoreciendo así su adecuado manejo diagnóstico-terapéutico. (AU)

Kimura’s disease is a rare benign inflammatory disorder of unknown etiology that mainly affects individuals of Asian origin. Clinically it manifests as subcutaneous, painless masses, especially in the head and neck area. It is usually accompanied by lymphadenopathies and an increase in eosinophil and IgE levels in peripheral blood. A case of Kimura’s disease is presented, diagnosed in a Caucasian woman after the excision-biopsy of a large mandibular mass. Describing this pathology will help to include it in the differential diagnosis of masses, especially at the cervico-facial area, thus favoring its adequate diagnostic-therapeutic management. (AU)

A different starting line for allergic march: food protein-induced allergic proctocolitis

Objective: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. Methods: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. Results: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively). In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). Conclusions: Patients with FPIAP may develop allergic diseases as well as FGID in the long term (AU)

Evaluating the influence of cold plasma bubbling on protein structure and allergenicity in sesame milk

Background: Sesame is a traditional oilseed comprising essential amino acids. However, the presence of allergens in sesame is a significant problem in its consumption; thus, this study attempted to reduce these allergens in sesame oilseeds.Objective: The present study aimed to evaluate the effect of cold plasma processing on structural changes in proteins, and thereby the alteration of allergenicity in sesame milk. Method: Sesame milk (300 mL) was processed using atmospheric pressure plasma bubbling unit (dielectric barrier discharge, power: 200 V, and airflow rate: 16.6 mL/min) at different exposure times (10, 20, and 30 min).Results: The efficiency of plasma-bubbling unit as measured by electron paramagnetic resonance in terms of producing reactive hydroxyl (OH) radicals proved that generation of reactive species increased with exposure time. Further, the plasma-processed sesame milk subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis and differential scanning calorimetery analysis revealed that plasma bubbling increased the oxidation of proteins with respect to bubbling time. The structural analysis by Fourier transform infrared spectroscopy and circular dichroism revealed that the secondary structure of proteins was altered after plasma application. This change in the protein structure helped in changing the immunoglobulin E (IgE)-binding epitopes of the protein, which in turn reduced the allergen-binding capacity by 23% at 20-min plasma bubbling as determined by the sandwich-type enzyme-linked immunosorbent assay. However, 30-min plasma bubbling intended to increase allergenicity, possibly because of increase in IgE binding due to the generation of neo epitopes.Conclusion: These changes proved that plasma bubbling is a promising technology in oxidizing protein structure, and thereby reducing the allergenicity of sesame milk... (AU)

Corilagin attenuates airway inflammation and collagen deposition in ovalbumin-induced asthmatic mice

Objective: To investigate the effects of corilagin on inflammation and collagen deposition in ovalbumin (OVA)-induced asthma mouse model and uncover the mechanism. Methods: We constructed a mouse model of OVA-induced asthma. Enzyme-linked-immunosorbent serologic assays were conducted to detect the effects of corilagin on cytokines and Immunoglobulin E (IgE) production. Hematoxylin and eosin staining was used to show pathological features in lung tissues. Masson trichrome assay was used to examine collagen deposition. In addition, the lung function was detected by mouse lung function apparatus. Immunoblot was used to confirm the mechanism. Results: Corilagin alleviates OVA-induced cytokine and IgE production. In addition, corilagin alleviates OVA-induced pathological changes and collagen deposition in lung tissues. Corilagin also suppressed airway resistance and lung function in mice. Mechanically, corilagin activated the adenosine monophosphate-activated protein kinase (AMPK) pathway in lung tissues. Conclusion: Corilagin attenuates airway inflammation and collagen deposition in OVA-induced asthmatic mice via AMPK pathway (AU)

Comparison of Intact Allergen Extracts and Allergoids For Subcutaneous Immunotherapy: The Effect of Chemical Modification Differs Both Between Species and Between Individual Allergen Molecules

Background: Allergen products for subcutaneous immunotherapy (SCIT) contain intact allergen extracts or chemically modified allergoids. Chemical modification was introduced to reduce allergenicity while retaining immunogenicity and thereby enable safer and more efficient allergy immunotherapy. Methods: Experimental allergoids were produced from intact allergen extract for birch, grass, and house dust mite (HDM) to evaluate the effects of chemical modification. Preparations were compared with commercial allergoids and analyzed using SDS-PAGE/immunoblotting, IgE-inhibition assays, and crossed immunoelectrophoresis (CIE). Dermatophagoides pteronyssinus (Der p) vaccines were also tested for protease activity and immunizing capacity in a mouse model. Results: The composition of IgE-binding epitopes in allergoids differed from that of intact allergen vaccines. Birch and grass allergoids produced smears of protein aggregates on SDS-PAGE, whereas intact allergen preparations showed distinct protein bands as expected. Der p allergoid vaccines, however, showed a distinct protein band corresponding to major allergen Der p 1 in both SDS-PAGE and CIE analysis, and commercial Der p allergoid vaccines showed Der p 1–related cysteine protease activity. Conclusion: Allergoids and intact allergen preparations differ with respect to the composition of IgE-binding epitopes. However, chemical cross-linking does not affect every allergen molecule to the same degree. Der p 1, for example, remains largely unmodified. Furthermore, the investigational HDM allergoid vaccines showed reduced and delayed immune responses when used for immunization of mice (AU)

Antecedentes: Los productos de alérgenos para inmunoterapia subcutánea (SCIT) contienen extractos de alérgenos intactos o alergoides modificados químicamente. En este trabajo se ha hecho una modificación química para reducir la alergenicidad a la vez que se conservaba la inmunogenicidad, y por lo tanto, permitir una inmunoterapia más segura y eficiente. Métodos: Se produjeron alergoides experimentales a partir de extracto de alérgeno intacto para abedul, hierba y ácaros del polvo doméstico (HDM) y se evaluaron los efectos de la modificación química realizada. Las preparaciones se compararon con alergoides comerciales y se analizaron mediante SDS-PAGE/inmunotransferencia, ensayos de inhibición de IgE e inmunoelectroforesis cruzada (CIE). Las vacunas de Dermatophagoides pteronyssinus (Der p) también se probaron para determinar la actividad de la proteasa y la capacidad de inmunización en un modelo de ratón. Resultados: La composición de los epítopos de unión a IgE en los alergoides difería de las vacunas de alérgenos intactas. Los alergoides de hierba y abedul produjeron manchas de agregados de proteínas en el SDS-PAGE, mientras que las preparaciones de alérgenos intactos mostraron distintas bandas de proteínas como se esperaba. Las vacunas alergoides Der p, sin embargo, mostraron una banda de proteína distinta de la correspondiente al alérgeno principal Der p 1 en los análisis SDS-PAGE y CIE. Las vacunas alergoides comerciales Der p mostraron actividad de cisteína proteasa relacionada con Der p 1.Conclusión: Los alergoides y las preparaciones de alérgenos intactos difieren con respecto a la composición de los epítopos de unión a IgE; sin embargo, el entrecruzamiento químico no afecta a todas las moléculas de alérgenos de un modo similar. Der p 1, por ejemplo, permanece prácticamente sin modificar. Además, las vacunas alergoides de HDM produjeron respuestas inmunitarias reducidas y tardías cuando se usaron para la inmunización de ratones (AU)

Clinical and Immunological Characterization of Perilla Seed Allergy in Children

Background: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergy are limited to a few case reports worldwide, and there is currently no diagnostic test for this allergy. Objective: Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. Methods: Twenty-one children with clinical perilla seed allergy were enrolled from 2 tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) and an IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of perilla seed allergy. IgE immunoblotting was performed to identify putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. SPT was performed with perilla seed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31-35, and 14-16 kDa bound to the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these 3 protein fractions showed 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. Conclusion: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds (AU)

Antecedentes: Las semillas de perilla pueden causar reacciones alérgicas inmediatas. Sin embargo, existen escasos estudios, limitados a escasos casos clínicos, sin que existan pruebas diagnósticas para esta alergia alimentaria.Objetivo: El objetivo de este trabajo es analizar las características clínicas e inmunológicas de los pacientes con alergia a semillas de perilla e identificar los alérgenos responsables con el fin de desarrollar nuevos métodos diagnósticos. Métodos: Se reclutaron 21 niños con alergia a semillas de perilla procedentes de dos hospitales entre septiembre de 2016 y 2019. Se realizaron prick test y determinación de IgE específica in vitro mediante ELISA utilizando un extracto de perilla. Igualmente se realizó immunoblotting para identificar los componentes alergénicos y determinar su composición mediante cromatografía líquida y espectometría de masas (LC-MS/MS). Resultados: Los niños con alergia a perilla tienen una mediana de edad de 3 años. El 28,6% de estos niños presentaron anafilaxia. Se realizó prick test con el extracto de perilla en 15/21 niños con resultado positivo en todos ellos. La IgE específica in vitro mediante ELISA fue positiva en el 85,7% de los casos. Más del 50% de los niños reconocían proteínas de 50, 31–35 y 14–16 kDa. El análisis mediante LC-MS/MS de estas tres fracciones identificó 8 proteínas diferentes, incluyendo una oleosina (Accession No. 9963891), como posibles alérgenos. Conclusiones: Este trabajo describe las características clínicas e inmunológicas de 21 niños con alergia a semillas de perilla. Nuestros resultados sugieren que una oleosina es uno de los alérgenos mayores en los pacientes con alergia a semillas de perilla (AU)

High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of –3.84 and –3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma (AU)

Relationship between exhaled nitric oxide and biomarkers of atopy in children and adolescents with allergic rhinitis

Introduction: Measurement of the exhaled nitric oxide fraction (FeNO) has been proposed as an indirect and non-invasive method to detect eosinophilic airway inflammation. Allergic rhinitis (AR) is frequently associated with high levels of FeNO. Allergic sensitization can contribute to the recruitment of eosinophils in the airway and the consequent increase in FeNO.ObjectiveTo correlate FeNO values with inflammatory and atopic sensitization biomarkers in patients with AR.Patients and methodsObservational, analytical, cross-sectional study. Children and adolescents with AR without asthma were included. FeNO, blood eosinophil count, total serum IgE were determined and skin tests with aeroallergens were performed by calculating the scores for PPC1 (number of positive allergens), STS2 (sum of millimeters of positive papules) and the atopy index (ratio between STS2/STS1). Spearman's correlation test was used between FeNO and variables of inflammation and atopy.ResultsTwenty-eight patients between 6 and 17 years old were included. There was a significant positive correlation between FeNO and blood eosinophils (r=.38; p=.047) and between FeNO and the atopy index (r=.40; p=.03). No correlation was found between FeNO and total serum IgE (r=.24; p=.21), STS1 (r=.20; p=.32) and STS2 (r=.34; p=.08).ConclusionIn children and adolescents with AR, FeNO was correlated with the atopy index and the blood eosinophil count. These last biomarkers could be used as alternatives for FeNO as biomarkers of lower airway inflammation in patients with AR. (AU)

Antecedentes: La determinación de la fracción exhalada de óxido nítrico (FeNO) ha sido propuesta como un método indirecto no invasivo para detectar la inflamación eosinofílica de la vía aérea. La rinitis alérgica (RA) se asocia frecuentemente con la FeNO elevada. La sensibilización a alérgenos puede contribuir al reclutamiento de eosinófilos en la vía aérea y el consiguiente incremento de la FeNO.ObjetivosCorrelacionar los valores de la FeNO con los biomarcadores inflamatorios y de sensibilización atópica en los pacientes con RA.Pacientes y métodosEstudio observacional, analítico y transversal. Se incluyeron niños y adolescentes con RA, sin asma. Se determinó la FeNO, el recuento de eosinófilos en sangre, la IgE sérica total, y se realizaron pruebas cutáneas con aeroalérgenos calificando los puntajes PPC1 (número de alérgenos positivos), PPC2 (suma de los milímetros de las pápulas positivas) y el índice de atopia (cociente entre milímetros de pápulas positivas/número de antígenos positivos). Se utilizó la prueba de correlación de Spearman entre la FeNO y las variables de inflamación y atopia.ResultadosSe incluyeron 28 pacientes entre 6 y 17 años. Se comprobó una correlación positiva significativa entre la FeNO y los eosinófilos en sangre (r=0,38; p=0,047), y el índice de atopia (r=0,40; p=0,03). No hubo correlación entre la FeNO con IgE sérica total (r=0,24; p=0,21) y con PPC1 (r=0,20; p=0,32) y PPC2 (r=0,34; p=0,08).ConclusionesEn niños y adolescentes con RA, la FeNO se correlacionó con el recuento de eosinófilos hemáticos y el índice de atopia. Estos últimos podrían utilizarse como sustitutos de la FeNO como biomarcadores de inflamación bronquial en pacientes con RA. (AU)

Study on the antipruritic mechanism of Zanthoxylum bungeanum and Zanthoxylum schinifolium volatile oil on chronic eczema based on H1R and PAR-2 mediated GRPR pathway

Objective: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium. Methods: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochem-istry, Western blot, and QRT-PCR.Results: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the patho-logical manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched (AU)

Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model

Background: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa character-ized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchy-mal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti-inflammatory potential in treating AR. Objective: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model.Material and Methods: The AR murine model was induced by repeated sensitization and chal-lenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated.Results: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symp-toms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa (AU)