The insight into house dust mites: which Dermatophagoides pteronyssinus proteins and cross-reactive allergens play pivotal role in sensitization among Polish patients with suspicion of allergy?

IntroductionMicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitization to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitization in childhood asthma.MethodsSerum samples from 1,126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs. We first divided according to HDM sensitization, and then tested whether miRNAs were differentially expressed (DE) between the two groups. Gene enrichment analysis for target genes of the DE miRNAs was then performed to identify potential causal pathways. A replication analysis was performed in the Childhood Asthma Management Program (CAMP), in which expression data of 258 miRNAs in 491 children were available. A mediation analysis was conducted to discern relationships between miRNA and phenotype differences according to HDM sensitization in GACRS cohort.ResultsThere were 906 (80.5%) and 220 (19.5%) subjects in the GACRS HDM+ and HDM- groups. Compared with HDM- participants, those in the HDM+ group were more likely to be severe in variables including pulmonary function, oral corticosteroids use, and blood tests. A total of 17 miRNAs were differentially expressed (p < 0.05) between the two groups. with miR-642a-3p, let-7c-5p, and miR-107 most significantly associated with HDM sensitization. In CAMP, there were 39 DE miRNAs and increased expression of miR-107 in HDM+ children were replicated in this cohort. In both GACRS and CAMP, the cadherin-binding pathway was enriched in an analysis of target genes for DE miRNA. In a mediation analysis, miR-107 showed significant indirect effects on eosinophil count and total IgE that were mediated by HDM sensitization.ConclusionIn children with asthma, miR-107 is associated with HDM sensitization. Further, miR-107 was indirectly associated with total IgE and eosinophil count through HDM sensitization.

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS)

The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.

Underestimation of house dust mite–specific IgE with extract-based ImmunoCAPs compared with molecular ImmunoCAPs

Background: We previously found that allergic rhinitis patients with an isolated pollen sensitization responded more strongly to a nasal provocation with grass pollen (GP) than patients who had an additional house dust mite (HDM) sensitization. To elucidate this phenomenon, we investigated the dynamics of Foxp3+CD4+ T lymphocytes in allergic rhinitis patients with distinct allergen sensitizations. Methods: Three groups of allergic rhinitis patients with skin prick test confirmed allergic sensitizations were investigated and compared to 14 healthy controls: 14 subjects with an isolated grass pollen sensitization (Mono-GP); 9 subjects with isolated housedust mite sensitization (Mono-HDM); 29 subjects with grass pollen and house dust mite sensitization (poly-sensitized). Subjects in the Mono-GP group were challenged with grass pollen extract, subjects in the Mono-HDM group were challenged with house dust mite extract, subjects in the poly-sensitized group and the healthy controls were randomly challenged with either grass pollen or house dust mite. Nasal biopsies were taken before and after nasal provocation. We compared the distribution of FoxP3+CD4+ cells in nasal biopsies before and after nasal provocation using immunohistochemistry. Results: There was no difference in the number of FoxP3+CD4+ cells between healthy and the three allergic groups at baseline.Nasal provocation did result in an increase in eosinophils in the three allergic groups, but did not result in a change in the number of FoxP3+CD4+ cells in any of the groups or induced differences between any of the groups. Conclusion: Clinical differences in the response between mono-GP and multiple-sensitized allergic individuals are not related to differences in the number of regulatory T cells in the nasal mucosa.

We previously found that allergic rhinitis patients with an isolated pollen sensitization responded more strongly to a nasal provocation with grass pollen (GP) than patients who had an additional house dust mite (HDM) sensitization. To elucidate this phenomenon, we investigated the dynamics of Foxp3+CD4+ T lymphocytes in allergic rhinitis patients with distinct allergen sensitizations. Three groups of allergic rhinitis patients with skin prick test confirmed allergic sensitizations were investigated and compared to 14 healthy controls: 14 subjects with an isolated grass pollen sensitization (Mono-GP); 9 subjects with isolated housedust mite sensitization (Mono-HDM); 29 subjects with grass pollen and house dust mite sensitization (poly-sensitized). Subjects in the Mono-GP group were challenged with grass pollen extract, subjects in the Mono-HDM group were challenged with house dust mite extract, subjects in the poly-sensitized group and the healthy controls were randomly challenged with either grass pollen or house dust mite. Nasal biopsies were taken before and after nasal provocation. We compared the distribution of FoxP3+CD4+ cells in nasal biopsies before and after nasal provocation using immunohistochemistry. There was no difference in the number of FoxP3+CD4+ cells between healthy and the three allergic groups at baseline.Nasal provocation did result in an increase in eosinophils in the three allergic groups, but did not result in a change in the number of FoxP3+CD4+ cells in any of the groups or induced differences between any of the groups. Clinical differences in the response between mono-GP and multiple-sensitized allergic individuals are not related to differences in the number of regulatory T cells in the nasal mucosa.

Objective: Chronic urticaria (CU), which is mostly idiopathic, may also be a sign of an allergic or systemic disease. A variety of diseases and allergens that accompany CU have been reported in various studies. The aim of this study was to investigate the factors that play a role in the etiology of CU.Materials and Methods: The demographic and clinical data from 302 patients – aged over 18 years - who were being monitored for CU were recorded. Several tests were performed to analyze comorbidities such as infection, malignancy, and autoimmune and rheumatic diseases. Skin Prick Test (SPT) results and questionnaires were reviewed.Results: Two hundred and thirteen out of the 302 patients with a mean age of 40.26±14.3 years were females. The duration of CU was 43.30±62.60 months and 42.9% of the patients had comorbidities. The most common disease was autoimmune thyroiditis (13.9%). Fifty-five percent of the patients were sensitive to inhalant allergens, and 5% exhibited allergen positivity for food. The most common allergens were house (43.7%) dust mites. Allergen positivity was 37.2% in those with comorbidities, while it was 62.8% in those without any comorbidities and this relationship was statistically significant (p<0.05).Conclusion: This study showed that there was an association between house dust mite and CU dust sensitivity. House dust mite sensitivity may trigger CU.

BackgroundThe relationship between atopic dermatitis (AD) and low vitamin D levels has been studied. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. However, the effect of vitamin D on house dust mite (HDM) sensitization in patients with AD has not been established.ObjectiveWe investigated the association between vitamin D levels and HDM sensitization according to AD severity.MethodsIn total, 80 patients (43 men and 37 women) with AD were included. We classified AD severity using Rajka and Langeland scores. Laboratory tests included serum 25-hydroxyvitamin D3, total immunoglobulin E (IgE), and specific IgE antibody titer against Dermatophagoides farinae and D. pteronyssinus.ResultsThere were no differences in vitamin D levels between the mild or moderate AD and severe AD groups. In the severe AD group, high HDM sensitization group had lower serum vitamin D levels compared to low HDM sensitization group with statistical significance. In addition, a significant negative correlation was found between vitamin D levels and HDM sensitization in the severe AD group.ConclusionOur results demonstrate that low vitamin D levels may link to high HDM sensitization in patients with the severe AD. Further elucidation of the role of vitamin D in HDM sensitization may hold profound implications for the prevention and treatment of AD.

Home gas appliance use has been associated with child respiratory illness but prospective data on the relationship between infant exposure and the development of child allergic disease has not been readily available. (a) To determine if home gas appliance use is associated with increased risk of house dust mite (HDM) sensitization. (b) To examine whether any association between current home gas use and airway obstruction is influenced by HDM sensitization. an 8-year follow-up birth cohort study of children born during 1988 and 1989. a population-based sample (n = 498) of children who participated in the Tasmanian Infant Health Survey (TIHS) and resided in Northern Tasmania in 1997 (84% of eligible children). (a) Skin prick test reaction to nine allergens, including Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). (b) Spirometric lung function indices, including forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The relative risk for home gas appliance use at 1 month of age and HDM sensitization was 1.98 (1.04, 3.79) in a cohort analysis with confounder matching. Current home gas use was also associated with HDM sensitization (ARR 1.73 (1.43, 2.76)). Current home gas use was related to a stronger (P = 0.006) reduction in the FEV(1) : FVC ratio among HDM-sensitive children (adjusted difference - 6.2% (- 10.0 to - 2.4)) than non-HDM-sensitive children (adjusted difference - 0.3% (- 2.5 to 1.8)). Indoor pollutants from gas combustion may increase the likelihood of initial sensitization to HDM and play a role in the development of atopic asthma. HDM-sensitized children may be more vulnerable to indoor pollutant-induced airway obstruction. The ability of this study to detect such effects may partly reflect unflued gas appliance use among this sample.

Asthma is commonly described as an atopic disease in childhood, but some cases of this disorder do not fit this description. The aim of this study was to evaluate the frequency of atopy, asthma, and sensitization to house dust mites in children with allergic symptoms. This study was performed at the Severance Hospital of Yonsei University with patients who visited the allergy clinic for evaluation of nonspecific upper respiratory symptoms, typical symptoms of asthma, or a general health workup. The patients were divided into three age groups: 0-3 years (group 1), 4-7 years (group 2), and 8-12 years (group 3). Of the 1,244 children examined, 844 (67.8%) were atopic and 400 (32.2%) were non-atopic. The frequency of atopy and asthma increased with age. Asthma was diagnosed in the same proportion (64%) of atopic and non-atopic children. As risk factors for asthma symptoms, the positive values of house dust mite (HDM) sensitivity were significantly increased in groups 1, 2, and 3 to 53.5%, 68.9%, and 80.2%, respectively. A significant difference between the percentage of asthmatics sensitized to HDM and that of asthmatics not sensitized to HDM was found only in group 3. In conclusion, asthma is related to atopy with increasing age, and house dust mite sensitization seems to be an important determinant of asthma in older children in Korea.

Background There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. Objective The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. Material and Methods This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). Results A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. Conclusions In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Bronchial allergen provocation (BAP) is an established tool for the diagnosis of allergy in patients with asthma, but its use is limited by the potential risk of severe asthmatic reactions. Nasal provocation testing (NPT) may be an alternative safe method and does not require sophisticated equipment. The aim of this prospective study was to evaluate the concordance of both methods in patients with asthma and house dust mite (HDM) sensitization. A total of 112 patients with HDM sensitization underwent BAP and had the following parameters analysed: decrease in FEV1, exhaled NO, and total and specific IgE. Within 12weeks, NPT with HDM was performed in 74 patients with a median age of 9years (range, 5-16years). The results were evaluated using the Lebel score which quantifies major symptoms like rhinorrhea, nasal obstruction, sneezes and minor symptoms, such as pruritus, conjunctivitis and pharyngitis. Fifty-seven of 74 patients had an early asthmatic reaction, of which 41 were identified using the Lebel score. The Lebel score had a sensitivity of 71.9% and a positive predictive value (PPV) of 89.1%. In addition, an eNO≥10ppb (AUC 0.78), a specific IgE Dermatophagoïdes pteronyssinus≥25.6 kU/L (AUC 0.76) and a specific IgE Dermatophagoïdes farinae≥6.6 kU/L (AUC 0.78) were good predictors of an early asthmatic reaction. A sequential use of NPT prior to BAP is justified to establish the relevance of HDM allergy. In patients with a negative NPT, BAP is still recommended to rule out a HDM-induced asthmatic reaction.

Allergen sensitization differs according to countries and regions. Understanding the characteristics of allergen sensitization in one's own country is useful for the treatment of patients with allergic diseases. Recently, Japanese cedar pollen (JCP) sensitization is increasing in young Japanese children. Therefore, we evaluated allergen sensitization patterns in under 60-month-old Japanese recurrent wheezers using multiple allergen tests. Allergen tests for 204 Japanese recurrent wheezers between April 2010 and April 2016 were reviewed. Children were divided into 10 groups by age, in 6-month intervals, from 0 months and analyzed by age group. Seventy five percent of children were diagnosed as bronchial asthma. Children under 12-months showed sensitization to food allergens, such as egg white (13.3%) and cow's milk (3.3%), and no sensitization to inhaled allergens. However, house dust mite (HDM) and JCP sensitization increased significantly in children 1 to 2 year of age (HDM; 7.7-32.1%, JCP; 3.9-17.9%) and both sensitization increased to most frequent in children over 36 months of age. JCP sensitization was also frequently detected in children with HDM sensitization (47.1%). Sensitization to inhaled allergens was significantly increased in Japanese recurrent wheezers over 12 months of age and sensitization to HDM and JCP increased to most frequent over 36 months of age. JCP sensitization was established from early childhood and detected frequently in Japanese recurrent wheezers under 60 months of age. These characteristics are the same with HDM sensitization.

Shellfish allergy is more prevalent in South-East Asia (~5%1 ) than in Western populations (e.g. United States ~2-3%.2 ). Typically commencing in late childhood, it is the leading cause of anaphylaxis in adolescents and adults in Asia. Cross-sectional studies have demonstrated a high correlation between shellfish and house dust mite (HDM) sensitization in warm, humid climates and urban environments where HDM are ubiquitous. The major shellfish allergen, tropomyosin, shares ~80% structural homology with HDM tropomyosin, and primary sensitization to dust mite tropomyosin has been hypothesized to induce cross-sensitization to shellfish.

Allergic diseases in children are influenced by gene-environment interactions. Although advanced parental age has been associated with genetic and epigenetic changes, its relationship with childhood allergy risk remains unclear. To examine the association between parental age at childbirth and the risk of allergic diseases in early childhood. This nationwide, multicenter, population-based, prospective birth cohort study used data from the Japan Environment and Children's Study (JECS). Participants were enrolled at 15 regional centers in Japan between January 2011 and March 2014, with follow-up data collected at child ages 1, 2, and 4 years. The present analysis was conducted from July 8, 2024, to February 4, 2025. Eligible participants were singleton live births with data on parental age and allergic outcomes. Physician-diagnosed allergy outcomes were collected via parental report. House dust mite (HDM) sensitization was assessed in a subcohort. The primary outcomes were physician-diagnosed food allergy, wheeze, asthma, and eczema at ages 1, 2, and 4 years. The secondary outcome was HDM sensitization at ages 2 and 4 years. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression after multiple imputation for missing values. A total of 34 942 mother-child pairs were included; the mean (SD) maternal age at entry was 31.0 (4.7) years, and 17 892 mothers (51.2%) had a medical allergy history. The prevalence of food allergy at age 1 year was 6.6% (95% CI, 6.4%-6.9%), decreasing with maternal age. Compared with children of mothers aged 25 to 29 years, those of mothers aged 35 to 39 years (OR, 0.79; 95% CI, 0.70-0.90) and aged 40 years and older (OR, 0.59; 95% CI, 0.44-0.79) had lower odds of food allergy. Children of parents both aged 35 years or older had lower odds of wheezing at age 4 years (OR, 0.89; 95% CI, 0.82-0.95). HDM was assessed in 1991 children at age 2 years and 1840 children at age 4 years, and children of older mothers also had lower odds of HDM sensitization (children of mothers aged 30-34 years, OR, 0.76; 95% CI, 0.59-0.98; children of mothers aged 35-39 years, OR, 0.68; 95% CI, 0.50-0.91). In this cohort study of 34 942 mother-child pairs, children of older mothers had reduced odds of food allergy, wheezing, and HDM sensitization in early childhood, suggesting that advanced maternal age may be protective against the development of allergic diseases in early childhood.