Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Artemisia Pollen Extracts Exposed to Diesel Exhaust Enhance Airway Inflammation and Immunological Imbalance in Asthmatic Mice Model.

BACKGROUND: Vehicle-induced air pollution may increase the prevalence and severity of asthma. Pollens are important sources of outdoor allergens associated with asthma. Outdoor pollution may influence the structure of pollen grains, resulting in enhanced immune reactions. OBJECTIVE: This study aims to investigate the impact that artemisia pollen extracts exposed to diesel emissions (APEDE) may induce - allergic airway inflammation, pulmonary pathology and immune imbalance - in mice. METHODS: Sixty male Balb/c mice were equally randomized into 5 groups, sensitized with 30 µL artemisia pollen extracts (APE) or APEDE adsorbed on 2 mg aluminum hydroxide gel by intraperitoneal injection on day 0, 7, 14, and 22, and challenged intranasally once per day with 30 µL APE or APEDE from day 29 to 36. The controlling group used phosphate-buffered saline as control. RESULTS: In mice immunized and challenged by APEDE, the clinical phenotype of eosinophils, neutrophils in bronchoalveolar lavage fluid (BALF), tracheal wall thickness, airway smooth muscle thickness and airway resistance increased significantly. Pathophysiological parameters such as interleukin (IL)-17A and tumour necrosis factor-α production in BALF and serum, and the ratio of Th17/Treg cells in CD4+ cells increased significantly, while IL-10 in BALF and serum and the ratio of Treg cells decreased significantly. It was further found that the expression of oxidative stress marker 3-nitrotyrosine (3-NT) and the activation of nuclear factor kappa B (NF-κB) were significantly increased. The correlation analysis showed that the expression of 3-NT was positively correlated with the activation of NF-κB. CONCLUSION: Our findings suggested that pollens exposed to diesel exhaust enhance allergic responses, which may contribute to an increased prevalence of allergic diseases in urban environments with serious exhaust emissions.

The prevalence and sex difference of allergen sensitization among adult patients with allergic diseases in Shanghai, China.

BACKGROUND: The worldwide prevalence of allergic diseases has increased during the last few decades, but it is not well known about the sensitization profiles of adult patients in Shanghai. OBJECTIVE: This study aimed to identify the prevalence and sex difference of allergen sensitization among adult with allergic diseases in Shanghai. METHODS: The sensitization profiles of 7,996 patients (18-60 yrs old) with allergic diseases at our center were retrospectively analyzed, based on the results of skin prick tests. The prevalence of various allergen, age and sex difference of allergen sensitization were investigated. RESULTS: The most common allergens were Dermatophagoides farinae (73.10%), Dermatophagoides pteronyssinus (72.21%) and Blomia tropicalis (53.10%), followed by Blattella germanica (31.18%), Periplaneta americana (27.75%), dog dander (24.96%), mixed molds (17.56%), and shrimp (17.02%). For the patients aged 18-30 yrs, mites and animal dander were most common allergen, whereas cockroaches and mixed molds for those aged over 40 yrs old. As for sex difference, males were more sensitive to Blomia tropicalis, cockroaches and mixed molds. Females were more sensitive to Dermatophagoides farinae and animal dander. CONCLUSIONS: The most common allergen in Shanghai are mites, cockroaches, and dog dander. There are sex and age difference on profiles of allergen sensitization.

The effect of stimuli on basophil-mediated atopic responses during asthmatic lying-in women and in newborns.

Morbidity from allergic diseases is increasing. Basophils play a critical role in systemic anaphylaxis and chronic allergic inflammation. The prenatal environment must be regarded as a possible early risk factor for allergic diseases in children. Our objective was to determine if basophils harvested from neonates genetically predisposed to atopic disease had different levels of CD63 expression and IL-4 release properties in response to various stimuli (peptidoglycan, Dermatophagoides farinae, hyperosmotic mannitol). Blood samples were collected from 16 asthmatic and 18 healthy women and their newborns. Peripheral blood basophil histamine was measured using the human basophil degranulation test (HBDT), whereas activation was assessed by flow cytometric measurement of CD63 expression on the cord blood basophil surface. IL-4 levels were quantified by ELISA following allergen stimulation. The basophil degranulation index (DI) in granulocytes harvested from the peripheral blood of asthmatic women was assessed following stimulation with peptidoglycan (PGN), Dermatophagoides farinae (Df ) extract, or hyperosmotic mannitol. The DI was significantly higher in atopic women than in healthy controls. Upregulation of CD63 on the cord blood basophil surface was also detected in response to these stimuli. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared to basophils purified from the controls. These data suggested that various stimuli play a role in augmenting allergic reactions via modulation of activated basophil cytokine secretion. It may require new methods to stabilize the basophils in allergic diseases.

The effect of peptidoglycan stimulation on basophil-mediated atopic responses during pregnancy and in newborns.

BACKGROUND: Toll-like receptor (TLR) molecules play critical roles in directing the course of atopic diseases by recognizing specific microbial products that activate immune effector cell function. OBJECTIVE: We determined if basophils harvested from neonates genetically predisposed to atopic disease had different levels of TLR2 expression and determined whether putative TLR2 ligands mediated cytokine secretion. METHODS: Blood samples were collected from 10 asthmatic and 12 healthy women and their newborns. Basophil histamine was measured using the human basophil degranulation test and TLR2 expression was determined using nucleic acid hybridization in situ and flow cytometry. IL-4 levels were quantified by ELISA following allergen stimulation. RESULTS: The basophil degranulation index (DI) in granulocytes harvested from peripheral blood of asthmatic women was assessed following stimulation with either peptidoglycan (PGN) or Dermatophagoides farinae (Df) extract. The DI was significantly higher in atopic women than in healthy controls. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared with basophils purified from children born to nonatopic controls. Finally, TLR2 expression at the protein and mRNA levels was upregulated in cord blood basophils from neonates born to mothers with asthma following stimulation with PGN but not Df. CONCLUSION: These data suggested that TLR2-mediated innate immune responses play a role in augmenting allergic reactions through the modulation of basophil cytokine secretion and histamine release. Microbial components may activate basophils through TLR2 (especially for genetically predisposed infants) to release cytokines associated with an increased incidence of allergic diseases.

Method for umbilical cord blood-derived basophils by FCM.

We have devised a method for the purification of human basophils from umbilical cord blood by FCM. Umbilical cord blood was collected from six healthy, full-term deliveries. After separation of red blood cells, mononuclear cells were isolated by Ficoll-Hypaque. Six samples followed by positive selection using flowcytometry (FCM) for CD203c(+)CD45(int+) cells. Purity and recovery of cells were measured. Purity and recovery of basophils by FCM with CD203c(+)CD45(int+) markers were 95.02 +/- 2.94% and 61.42 +/- 5.95%. Cell sorting for CD203c(+)CD45(int+) cells by FCM is an improved method for obtaining pure umbilical cord blood-derived basophils. We established cord blood-derived basophil purification technique as a source from which active basophils can be isolated for immunochemical characterization.

[Expression of T-bet, GATA-3 and FOXP3 mRNA in asthmatic peripheral blood mononuclear cells stimulated by Dermatophagoides farinae antigen].

OBJECTIVE: To study the expression of T-bet, GATA-3 and FOXP3 mRNA in asthmatic peripheral blood mononuclear cells (PBMC) before and after stimulation by Dermatophagoides farinae antigen (Df), and the relationship among the three transcription factors. METHODS: Twenty-five patients of asthma and 15 healthy controls were included. The mRNA levels of T-bet, GATA-3, and FOXP3 in PBMC before and after Df stimulation were detected by semiquantitative reverse transcription-polymerase chair reaction (RT-PCR). RESULTS: There was no statistical difference (t = 0.78, 0.38 respectively, all P > 0.05) in the levels of T-bet and FOXP3 mRNA between the patients (0.3 +/- 0.4, 0.42 +/- 0.24 respectively) and the healthy controls (0.4 +/- 0.3, 0.39 +/- 0.37 respectively). However, GATA-3 mRNA was statistically different (t = 2.27, P < 0.05) between the patients (1.0 +/- 0.3) and the healthy controls (0.8 +/- 0.3). After the stimulation of PBMC by Df, the levels of T-bet, GATA-3 and FOXP3 mRNA showed statistical difference (t = 2.30, 3.79, 2.08 respectively, P < 0.05, < 0.01, < 0.05 respectively) between the patients (0.33 +/- 0.39, 1.58 +/- 1.44, 0.11 +/- 0.32 respectively) and the healthy controls (0.03 +/- 0.40, 0.11 +/- 0.53, 0.43 +/- 0.66 respectively). The FOXP3 mRNA level in the asthmatics was negatively correlated with T-bet and GATA-3 mRNA (r = -0.46, P < 0.05, r = -0.62, P < 0.01 respectively). CONCLUSIONS: There are a predominant expression of GATA-3 and T-bet, but a decreased expression of FOXP3 in Df-stimulated PBMCs from patients with asthma.

[The specific IgE responses to three cockroach strains antigens in patients with asthma].

OBJECTIVE: The purpose of the present study was to determine the cross-reactive allergens from three strains of cockroach (Periplaneta americana, Periplaneta fuliginosa and Blattella germanica) by human serum specific IgE (sIgE) in allergic asthma. METHODS: The allergens were extracted from Periplaneta americana, Periplaneta fuliginosa and Blattella germanica respectively. Serum sIgE of allergic asthma was determined with ELISA. RESULTS: The sIgE positive rates to Periplaneta americana, Periplaneta fuliginosa and Blattella germanica were 23.5%, 16.0% and 14.0% respectively. The reactive coincidence rate between Periplaneta americana and Periplaneta fuliginosa was 74.0%. The reactive coincidence rate between Periplaneta americana and Blattella germanica was 73.5%. The reactive coincidence rate between Periplaneta fuliginosa and Blattella germanica was 85.0%. The sIgE positive rates of the head and the body of Periplaneta americana were 17.5% and 14.5% respectively. The sIgE positive rates of the head and the body of Periplaneta fuliginosa were 12.5% and 10.5% respectively. The reactive coincidence rate between head and body of Periplaneta americana was 86.0%. The reactive coincidence rate between head and body of Periplaneta fuliginosa was 88.0%. There were some cross-inhibition among the three strains of cockroach according to ELISA cross-inhibition test. CONCLUSION: Cockroach is one of the main allergens which cause allergic asthma. There exists significant cross-reactive allergic components in the three strains of cockroach and between the head and the body of Periplaneta fuliginosa and Periplaneta americana.