BACKGROUND: Increasing numbers of research have revealed an etiological association between peripheral blood markers and allergy. Nevertheless, whether these associations are causal and whether they vary among different allergic diseases and ethnicities remain unclear. METHODS: 32 peripheral biomarkers with consistent definition were collected from three nationwide biobanks (UK Biobank, FinnGen, and BioBank Japan). Summary-level data for asthma (n=774,328), dermatitis (n=880,733), and allergic rhinitis (n=893,300) were obtained from these biobanks. Mendelian randomization (MR) analyses and meta-analyses were applied to explore the generalizability and heterogeneity of causal effects among different allergic diseases and ethnicities. The clinical data (n=9,877) in China and US were collected to verify peripheral markers affecting allergy. RESULTS: The MR analyses provided consistent evidence for the causal effects of seven shared heritable factors (eosinophil, neutrophil, basophil, glomerular filtration rate, mean corpuscular hemoglobin concentration, platelet distribution width, and hematocrit) on broad allergic disease phenotype in both ethnic groups, three of which are new. These findings are further corroborated by our observational studies in China and US. Glucose showed a causal effect on allergy in Europeans while five factors, including c-reactive protein/CRP, LDL cholesterol/LDLC, total cholesterol/TC, hemoglobin A1c/Hb1Ac, and glucose, are important for East Asians. Moreover, we observed trans-ethnic evidence for the causal effects of five factors (CRP, white blood cell/WBC, total protein, albumin, and hemoglobin concentration) on asthma, two factors (aspartate aminotransferase and WBC) on dermatitis, and LDLC on allergic rhinitis, reflecting the etiological discrepancy among different allergic diseases. In East Asians, we also noticed the ethnic-specific causalities of triglyceride on asthma, alanine aminotransferase on dermatitis, and three factors (monocyte, albumin, and creatinine) on allergic rhinitis. CONCLUSIONS: Our results support the causal effects of 22 blood heritable factors on allergic diseases, providing novel insights into the comprehensive assessment of allergic risks and the design of universal and personalized interventions.

To the Editor,The proportion of the population with allergic diseases has increased rapidly in recent decades1, 2. In addition to affecting the quality of life, a significant economic burden of these diseases was transferred to society and the national health care system1. China is a large country with a rapidly developing economy, wide geography, and diverse climate and lifestyles, which may lead to significantly regional differences in the distribution of allergens. Although a series of studies have explored the prevalence of allergen sensitization in China, the majority of them focus on one part of geography in China3-5. In 2009, a study6 was conducted to estimate the prevalence of common aeroallergens among patients with allergic asthma and/or rhinitis in mainland China. Although the study investigated the differences of the prevalence in different regions of China, it divided China into only four geographical regions, which may neglect detailed information about the characteristics of sensitization prevalence in different places in China. In that study, the skin prick test (SPT) was used to detect the sensitization to allergens. The method has low accuracy for positive results because it is heavily affected by certain factors, such as the skill of the tester, reagent used, interpretation of results and so on. Our research has the following different characteristics compared with previous studies: 1) covering a variety of allergic diseases, 2) exploring both aeroallergens and food allergens simultaneously, 3) including a large set of data from all the seven regions of mainland China, and 4) using an internationally recognized method of sIgE testing, ImmunoCAP, to detect sensitization. These advantages may help us obtain more accurate and reliable results and conclusions.Here, we conducted a large multicenter study on the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization to the four most common food allergens (i.e., egg whites, cow’s milk, crab, and shrimp) and five aeroallergens (i.e., house dust mite, German cockroach, tree pollen mix, mold mix, dog dander) among 44156 patients with allergic symptoms in 52 cities from 26 provinces of all the seven geographical regions in mainland China from July 2015 to June 2018. The sIgE sensitization was tested by a certified third-party laboratory service provider with uniform and standardized procedures. This study was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (Approval number: GYFYY-2017-18). Details about the methods were in the supplementary materials .Our study showed that the overall prevalence of positive sIgE responses to the 9 allergens across mainland China from the highest to the lowest was 33.74% for house dust mites, 24.5% for cockroaches, 19.97% for shrimp, 17.31% for crab, 11.62% for cow’s milk, 10.92% for egg whites, 9.35% for tree pollen mix, 4.02% for dog dander and 3.92% for mold mix (Table 1 ). Our study confirmed that an observation shown in several previous studies based on certain specific areas in China3-5 that the positive cases in sIgE fell mainly in the two low classes (i.e., classes 1 and 2) was also held in all the seven regions in mainland China (Table 1 ).Our study revealed the distinctive patterns in the prevalence of allergen sensitization among regions, gender, age groups and seasons. Geographically, there is a significant difference in the prevalence among regions for all 9 allergens except for the mold mix (Table S1 ). House dust mites were the allergen with the highest prevalence of sensitization in all seven regions, with the highest in South China (40.79%) and the lowest in Northeast China (11.21%). Allergies to German cockroaches had a higher prevalence in southern regions (Southwest China, South China and East China) than in northern regions (North China and Northeast China). The prevalence of sIgE responses to dog dander was the highest in North China and was very close to each other in the southern regions. The prevalence of the egg whites and milk in Central China, East China and South China was higher than in Southwest China, North China and Northeast China, which means that patients living in eastern, coastal and/or southern areas were more sensitive to egg whites and cow’s milk. The prevalence of crab and shrimp sensitization in Southwest China and South China was higher than that in the northern regions (North China and Northeast China). The heatmap (Figure 1 ) displays the distribution of the prevalence of the sIgE response to allergens in different regions of mainland China.The prevalence of sensitization to all nine allergens was higher overall in males than in females (Table 1 and Figure S1 ) although that may not be true in each age group for each allergen as shown in the forest plot in Figure S1 . Our study showed that, whereas the sensitization to egg whites and milk was the highest in children, the sensitization to other allergens tended to be the highest in teenagers and young adults (Figure S2 ). Figure S3displays he prevalence pattern of allergens by months across years. The prevalence of dog dander and mold mix was very stable across months; however, the prevalence of other allergens fluctuated from January to December. The prevalence of house dust mites, German cockroach, shrimp and crab were higher in the summer months (from June to August) than in other months. The prevalence of tree pollen mix was much higher in April and October than in other months.This should be the first large study to investigate the prevalence of allergen sensitization in the patients with allergic symptoms from all the seven geographic regions of mainland China. Based on this study, we found that the prevalence of sIgE sensitization to allergens displayed obvious and distinctive patterns among regions, gender, age groups and seasons. The reasons for these patterns may include lifestyle factors, socioeconomic factors, genetic predispositions, climate, sexual hormones, cross-reactivity and so on3,4,6-9. Please refer to the supplementary materials for the detailed discussion on the factors that influenced these variations. Our findings may help clinicians find effective individualized treatments for unique patient groups and direct researchers to conduct further studies on the epidemiology of allergic diseases.

Background: The proportion of the population with allergic diseases has increased rapidly in recent decades. Studies on the prevalence of allergens contribute to the treatment and prevention of allergic diseases. Although many studies have been published on the prevalence of allergens in China, there are limited studies on the geographic distribution of allergens. Objective: The aim of this study was to explore the prevalence patterns of sensitization to allergens among patients with allergic diseases in all the seven geographic regions of mainland China. Methods: A large epidemiological study was conducted on the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization to the four most common food allergens and five aeroallergens among 44156 patients with allergic symptoms from 2015 to 2018. The data were analyzed using the chi-square test, and descriptive statistics, forest plots and geographic heatmaps. Results: First, house dust mites were the allergen with the highest prevalence of sensitization in all seven regions, with the highest in South China (40.79%) and the lowest prevalence in Northeast China (11.21%). The prevalence of allergens varied in different regions and seasons. Second, the prevalence of sensitization was significantly higher among male than female subjects. Third, except for egg whites and milk, which had the highest positive rates in children, sensitization to other allergens tended to be the highest in teenagers and young adults. Conclusions: Our findings could help clinical staff apply effective treatment to unique patient groups and direct researchers to conduct deeper studies on the epidemiology of allergic diseases.

Abstract: Background: The diagnosis of COVID-19 relies mainly on viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis. SARS-CoV-2-specific antibody detection is convenient, safe, and highly sensitive. IgM and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA, and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. Methods: COVID-19 patients, divided into a severe & critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA, and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results, and other data were recorded for all patients. Results: Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are better for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe & critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Conclusions: Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.