S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice.

Background: Allergic asthma is the most prevalent asthma phenotype and is associated with the disorders of immune cells and glycolysis. Macrophages are the most common type of immune cells in the lungs. Calprotectin (S100A8 and S100A9) are two pro-inflammatory molecules that target the Toll-like receptor 4 (TLR4) and are substantially increased in the serum of patients with severe asthma. This study aimed to determine the effects of S100A8/A9 on macrophage polarization and glycolysis associated with allergic asthma. Methods: To better understand the roles of S100A8 and S100A9 in the pathogenesis of allergic asthma, we used ovalbumin (OVA)-induced MH-S cells, and OVA-sensitized and challenged mouse models (wild-type male BALB/c mice). Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, flow cytometry, hematoxylin-eosin staining, and western blotting were performed. The glycolysis inhibitor 3-bromopyruvate (3-BP) was used to observe changes in glycolysis in mice. Results: We found knockdown of S100A8 or S100A9 in OVA-induced MH-S cells inhibited inflammatory cytokines, macrophage polarization biomarker expression, and pyroptosis cell proportion, but increased anti-inflammatory cytokine interleukin (IL)-10 mRNA; also, glycolysis was inhibited, as evidenced by decreased lactate and key enzyme expression; especially, knockdown of S100A8 or S100A9 inhibited the activity of TLR4/myeloid differentiation primary response gene 88 (MyD88)/Nuclear factor kappa-B (NF-κB) signaling pathway. Intervention with lipopolysaccharides (LPS) abolished the beneficial effects of S100A8 and S100A9 knockdown. The observation of OVA-sensitized and challenged mice showed that S100A8 or S100A9 knockdown promoted respiratory function, improved lung injury, and inhibited inflammation; knockdown of S100A8 or S100A9 also suppressed macrophage polarization, glycolysis levels, and activation of the TLR4/MyD88/NF-κB signaling pathway in the lung. Conversely, S100A9 overexpression exacerbated lung injury and inflammation, promoting macrophage polarization and glycolysis, which were antagonized by the glycolysis inhibitor 3-BP. Conclusion: S100A8 and S100A9 play critical roles in allergic asthma pathogenesis by promoting macrophage perturbation and glycolysis through the TLR4/MyD88/NF-κB signaling pathway. Inhibition of S100A8 and S100A9 may be a potential therapeutic strategy for allergic asthma.

Clinical characteristics of persistent or recurrent pneumonia combined with airway malacia in children.

OBJECTIVE: The aim of this study is to investigate the clinical characteristics and pathogens involved in persistent or recurrent pneumonia combined with airway malacia in children. METHODS: We retrospectively reviewed the information of children hospitalised with persistent or recurrent pneumonia, including clinical presentations, laboratory examination results and pathogens. RESULTS: A total of 554 patients were admitted, 285 (51.44%) of whom were found to have airway malacia. There were 78 (27.37%), 166 (58.25%) and 41 (14.39%) patients with mild, moderate and severe malacia, respectively. Patients with airway malacia were younger than those without malacia (6.0 vs. 12.0 months, p < 0.01) and were more likely to present with wheezing (75.07%), fever (34.39%), dyspnoea (28.77%), cyanosis (13.68%) and wheezing in the lungs (78.95%). The incidence of preterm delivery, oxygen therapy, paediatric intensive care unit (PICU) admission and mechanical ventilation was higher, and the hospital stay (11.0 vs. 10.0 days, p = 0.04) was longer in these patients than in those without malacia. Patients with severe airway malacia were more likely to undergo oxygen therapy, PICU admission, mechanical ventilation and have multiple malacia than were those with mild or moderate malacia. Mycoplasma pneumoniae (30.18%) was the most common pathogen. CONCLUSION: Severe airway malacia likely aggravates conditions combined with pneumonia. The proportion of multisite malacia was greater in severe airway malacia patients.

Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma.

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

miR-130b regulates B cell proliferation via CYLD-mediated NF-κB signaling.

Previous studies have revealed that B cell activation is regulated by various microRNAs(miRNAs). However, the role of microRNA-130b regulating B cell activation and apoptosis is still unclear. In the present study, we first found that the expression of miR-130b was the lowest in Pro/Pre-B cells and the highest in immature B cells. Besides, the expression of miR-130b decreased after activation in B cells. Through the immuno-phenotypic analysis of miR-130b transgenic and knockout mice, we found that miR-130b mainly promoted the proliferation of B cells and inhibited B cell apoptosis. Furthermore, we identified that Cyld, a tumor suppressor gene was the target gene of miR-130b in B cells. Besides, the Cyld-mediated NF-κB signaling was increased in miR-130b overexpressed B cells, which further explains the enhanced proliferation of B cells. In conclusion, we propose that miR-130b promotes B cell proliferation via Cyld-mediated NF-κB signaling, which provides a new theoretical basis for the molecular regulation of B cell activation.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Are we ready to face the next wave of RSV surge after the COVID-19 Omicron pandemic in China?

Background: China had its first wave of COVID-19 in 2020 and second wave of COVID-19 Omicron in 2022. The number of RSV cases decreased sharply in 2020 and 2022. Investigation of the resurge of RSV infections after the first wave of COVID-19 will guide us to take preventive actions before the resurge of RSV infections after the second wave of COVID-19 Omicron. Methods: We analysed epidemiological and clinical data of 59934 patients with lower respiratory tract infections (LRTI) from a prospective long-term cohort surveillance programme in Suzhou, China, collected from February 2016 to January 2022. The annual incidence of RSV infection in children aged<16 years in 2020 and 2021 was compared with the pre-pandemic years 2016 to 2019. We also compared the clinical characteristics, and RSV-related ICU admissions between pre-pandemic years and 2021. Results: Among children with LRTI, the positive rate of RSV increased by 70.7% in 2021 compared to the average level in the pre-pandemic years. The RSV resurge in 2021 was most prominently in children aged 2-4 years (a significant rise compared with the expected value 149.1%; 95%CI, 67.7% to 378%, P<.01). The percentage of RSV-related ICU admissions decreased in 2021 (3.2% vs 6.7%, P<0.01). The death rate of RSV infections in 2021 was 0.2%, while that in pre-pandemic years was only 0.02%. RSV-associated death in immunocompetent children (complicated by necrotizing encephalitis) was firstly occurred in 2021. Conclusions: Our findings raise concerns for RSV control in Southeast China after the COVID-19 pandemic especially for children aged 2-4 years. Although ICU admissions were significantly reduced in this resurgence, we could not ignore the increase of RSV-associated death.

Etiology and clinical features of infection-associated plastic bronchitis in children.

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.

Patterns of aeroallergen sensitization in asthma patients identified by latent class analysis: A cross-sectional study in China.

BACKGROUND: This cross-sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. METHODS: 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. RESULTS: Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: "High weed pollen and house dust mites (HDMs) sensitization" (8.87%), Class 2: "HDMs dominated sensitization" (38.38%), Class 3: "High HDMs and animal dander sensitization" (6.95%), Class 4: "Low/no aeroallergen sensitization" (45.80%). Western cohort: Class 1: "High weed pollen sensitization" (26.14%), Class 2: "High multi-pollen sensitization" (15.02%), Class 3: "HDMs-dominated sensitization" (10.33%), Class 4: "Low/no aeroallergen sensitization" (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. CONCLUSIONS: Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1.

Studies already revealed that some E3 ubiquitin ligases participated in the immune response after viral infection by regulating the type I interferon (IFN) pathway. Here, we demonstrated that type I interferon signaling enhanced the translocation of ETS1 to the nucleus and the promoter activity of E3 ubiquitin ligase DTX3L (deltex E3 ubiquitin ligase 3L) after virus infection and thus increased the expression of DTX3L. Further experiments suggested that DTX3L ubiquitinated TBK1 at K30 and K401 sites on K63-linked ubiquitination pathway. DTX3L was also necessary for mediating the phosphorylation of TBK1 through binding with the tyrosine kinase SRC: both together enhanced the activation of TBK1. Therefore, DTX3L, being an important positive-feedback regulator of type I interferon, exerted a key role in antiviral response. IMPORTANCE Our present study evaluated DTX3L as an antiviral molecule by promoting IFN production and establishing an IFN-ß-ETS1-DTX3L-TBK1 positive-feedback loop as a novel immunomodulatory step to enhance interferon signaling and inhibit respiratory syncytial virus (RSV) infection. Our finding enriches and complements the biological function of DTX3L and provides a new strategy to protect against lung diseases such as bronchiolitis and pneumonia that develop with RSV.

Pollen allergens sensitization characteristics and risk factors among allergy rhinitis of children in mainland China: A multicenter study.

Background: No comprehensive multicenter study of sensitization patterns among patients with allergic rhinitis (AR) to various common pollen allergens was available nationwide, and risks factors of pollen-induced allergic rhinitis (PiAR) in mainland China was unclear. This study aimed to fill this gap. Methods: A multicenter study was performed on 736 AR patients aged below 18 from four regions of mainland China. Patients completed a standardized questionnaire asking for the environmental risk factors and AR severity, and undertook skin prick tests (SPT) with 14 common pollen allergens. Findings: Among the 736 patients, 341 patients (46.33%) suffered at least one positive pollen allergen sensitization. The positive rate of pollen allergens was significantly higher in the high-age group (Damato et al., 2007; Wang et al., 2018; Luo et al., 2016; Demoly et al., 2011; Sampson and Albergo, 1984; Li et al., 2009; Luo et al., 2021; Ziska and Beggs, 2011; Melén et al., 2020; Jensen-Jarolim, 2017; Rönmark et al., 2017; Ge et al., 2017) [6-17] than the low-age group ( ≤ 5), while no significant difference was found between the sexes. The sensitizations to pollen allergens varied widely among four geographical areas. The positive rate was higher in north China and west China than in east China, and south China had the lowest positive rate. The region of residence, ages, ethnic minorities, history of pollen exposure, the material of living room floor and material of pillow were statistically significant risks of PiAR. Interpretation: This study provides new insights into the pollen allergens sensitization characteristics in AR and the factors affecting PiAR in mainland China.

Epidemiological and clinical characteristics of human rhinovirus caused bronchiolitis in children in Southeast China.

BACKGROUND: Human rhinovirus (hRV) is a critical viral pathogen implicated in bronchiolitis in children. However, there is no study on hRV bronchiolitis in children from Southeast China. The aim of this study was to determine the incidence and clinical features of hRV bronchiolitis in Southeast China. METHODS: The study was carried out in Children's Hospital of Soochow University on children admitted with the diagnosis of bronchiolitis from January 2013 to December 2014. hRV was tested using reverse-transcription polymerase chain reaction. RESULTS: hRV was identified in 140 of 797 specimens (17.6%). hRV was detected with a highest rate in June and August. The hRV positive rate in patients younger than 6 months of age was significantly lower than that in other age groups (P<0.01). The most common radiological finding was hyperinflation (51.4%). Patients with hRV infection were older and more likely to have eczema than those with RSV. CONCLUSIONS: The hRV was an important viral pathogen associated with bronchiolitis in children with an epidemic peak in summer. Most of patients were between 6 to 24 months and with a high presence of eczema.

Cbl-b inhibited CD4+ T cell activation by regulating the expression of miR-99a/miR-125b.

The molecular regulation of T cell activation has always been a hot topic in immunology. It has been reported that Cbl-b inhibits T cell activation, but the specific molecular mechanism especially for transcriptional regulation has not been very clear so far. Our present study showed that ablation of Cbl-b resulted in the increased expression of miR-99a and miR-125b, and the antagonism of miR-99a or miR-125b could inhibit the Cbl-b-/- T cell over-activation partly. Further study demonstrated that Cbl-b could bind and ubiquitinate SHP-2 in the activated T cells. The activation of SHP-2 deficient T cells was significantly inhibited. Western blot showed that SHP-2 could dephosphorylate HOXA10, and HOXA10 could enter the nucleus under the stimulation of anti-CD3 antibody alone in Cbl-b deficient T cells. Luciferase reporter assay and CUT&Tag qPCR showed that HOXA10 could regulate the expression of miR-99a/miR-125b. Real-time PCR and western blot further indicated that miR-99a/miR-125b functioned on PI3K/AKT pathway to regulate T cell activation. In conclusion, our study demonstrated that Cbl-b ubiquitinated SHP-2 to arrest HOXA10-mediated CD4+ T cell activation by regulating the expression of miR-99a/miR-125b and their function on PI3K/AKT pathway, which might providing a new explanation for the regulation of T cell activation and potential new idea for autoimmune diseases and tumor immunotherapies.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

BACKGROUND: Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. METHODS: We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. RESULTS: LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. CONCLUSION: We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

[Association of Haemophilus influenzae infection with environmental and climatic factors in Suzhou, China]. / è‹å·žåœ°åŒºæµæ„Ÿå—œè¡€æ†èŒæ„ŸæŸ“ä¸ŽçŽ¯å¢ƒæ°”å€™çš„ç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.

Sensitization to Furry Animals in Patients with Suspected Allergic Disease in China: A Multicenter Study.

Purpose: An objective of this study was to investigate the allergen sensitization characteristics of cat, dog and horse dander in patients with suspected allergic diseases in different geographical regions of Chinese mainland. Patients and Methods: We invited 2377 patients aged 0-86 years with suspected allergic diseases to participate in a cross-sectional survey in 11 provinces in China. Combined with the questionnaires and animal-specific IgE levels, we analyzed the epidemiological characteristics and risk factors of furry animal sensitization in different regions and populations of Chinese Mainland. Results: Among the 2377 patients with suspected allergic diseases, 14.9% were sensitized to cat dander, 9.3% to dog dander and 5.5% to horse dander. Animal allergens mainly cause low-level sensitization (class 1-3). There was a significant correlation between cat, dog and horse dander allergen sIgE, with correlation coefficients (rs) all greater than 0.750. The majority (46.5%) of sIgE-positive patients were sensitized to at least two animal allergens simultaneously. The prevalence of these animals all showed a trend of increasing first and then decreasing with age, and all reached the peak in young adolescence. As for the geographical factors, the sensitization rate of cats and dogs in Western was significantly higher than that in Eastern (cat: 18.4% vs 9.2%, dog: 11.6% vs 5.5%, all P < 0.001), however, no significant differences were found in horses. Aged ≤6 years, living in Western, and high animal allergen exposure elevated the risk of cat or dog sensitization. Living on a lower floor (aOR: 0.56) was a protective factor for horse sensitization. Conclusion: In this representative sample of Chinese patients with suspected allergic diseases, there was an apparent geographic variation in sensitization to cats and dogs. Age factor and living in Western also had a significant impact on animal allergen sensitization rate.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Background: Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods: Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results: The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions: Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

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.