Cockroach Allergen Research Articles

Overcrowding and Hazardous Dwelling Condition Characteristics: A Systematic Search and Scoping Review of Relevance for Health

Crowding in dwellings is an important public health issue. We hypothesize that overcrowding may cause indirect health effects by adversely affecting the dwelling itself, for example, by increasing dampness leading to mold. We therefore performed a systematic search and a scoping review on overcrowding leading to dwelling condition characteristics of relevance for health. A literature search was performed using the PubMed and Scopus databases up to 5 March 2021. The search yielded 100 records with relevant information. We found that overcrowding is defined in numerous ways and often address "socially deprived" populations. Six studies report associations of overcrowding with at least one dwelling condition characteristic, namely lead, cadmium, microorganism distribution, dust mite and cockroach allergens in dust, cockroach infestation, peeling paint, and mold. One of the studies reports associations between several characteristics, e.g., association of mold with cleanliness and rodent infestation, and points out the common use of pesticides. Additional characteristics were extracted from the remaining 94 records, without data on statistical associations with overcrowding. Our review suggests that multiple potentially hazardous dwelling condition characteristics often coincide in overcrowded dwellings. The epidemiological attribution of health effects to any characteristic is therefore difficult. Causal relationships are even more difficult to establish, as overcrowding is also associated with a range of social and other circumstances that may affect health. The complexity should be considered by scientists and practitioners dealing with overcrowding in dwellings.

Sensitization characteristics of cockroach in Beijing area

Objective:To investigate the sensitization characteristics of cockroach in patients with allergic rhinitis（AR） and/or allergic asthma in Beijing area, and to provide basis for the prevention and treatment of cockroach sensitized population. Methods:Clinical data of patients with allergic rhinitis and/or asthma from January 2017 to December 2019 treated in the outpatient Department of Allergy of Beijing Shijitan Hospital were retrospectively analyzed.Skin prick test （SPT） was performed with cockroach allergen reagents. The cockroach sensitization of patients with different ages and diseases was compared, and the population distribution characteristics of cockroach sensitization were observed.Statistical analysis was performed using SAS 9.4 software. Results:A total of 9915 patients were enrolled in the end.The total positive rate of cockroach SPT was 24.79%（2458/9915）,with the highest positive rate （31.65%） in 15-19 years old group. The positive rate of SPT increased with age in patients less than 14 years old, while the positive rate of SPT was basically flat with age in patients more than 20 years old .The positive rate of cockroach SPT was 24.83% （2355/9484） in allergic rhinitis patients,26.38% （410/1554） in allergic asthma patients, and 27.34% （307/1123） in allergic rhinitis combined with asthma patients. Single cockroach SPT positive accounted for 9.64% （237/2458）, cockroach with other indoor inhalation allergens SPT positive accounted for 90.36% （2221/2458）. The positive SPT rates for combined Der f , Der p,house dust, cat dander, and dog dander were 74.25% （1825/2458）, 66.27% （1629/2458）, 58.99% （1450/2458）, 43.08% （1059/2458）, and 40.85% （1004/2458）, respectively.In allergic rhinitis，asthma，and allergic rhinitis combined with asthma，the cockroach SPT positive rate was higher in the adult group than that in juvenile group，and the difference of positive rate in allergic rhinitis group was statistically significant（25.81% vs 19.07%, P<0.001）.In the juvenile group, the positive rate of SPT in AR combined with asthma was higher than that in AR and that in asthma. Conclusion:Cockroach allergy in patients with AR and/or allergic asthma in Beijing is relatively high, most of them are sensitized by multiple inhalation allergens, and the sensitization degree of adults is higher than that of juvenile.

Genome assembly and annotation of Periplaneta americana reveal a comprehensive cockroach allergen profile.

One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information. To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana. A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50=151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction. The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.

CircS100A11 enhances M2a macrophage activation and lung inflammation in children with asthma.

Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined. The differential expression profiles of circRNAs were analyzed by microarray. The effects and mechanisms by which circRNAs influence macrophage activation were detected by quantitative real-time PCR, RNA immunoprecipitation assay, and chromatin immunoprecipitation assay, among others. The roles of circRNA and its host gene in asthma were tested in a cockroach allergen extract (CRE)-induced murine asthma model. We identified 372 circRNAs that were differentially expressed in PBMCs of children with asthma as compared with healthy controls. A circRNA with unknown function, circS100A11, was dominantly expressed in monocytes and significantly upregulated in children with asthma. circS100A11 facilitated M2a macrophage activation by enhancing translation of its host gene, S100A11, and exacerbated lung inflammation in a CRE-induced murine asthma model with macrophage-specific overexpression of circS100A11. Mechanistically, circS100A11 promoted S100A11 translation by competitively binding to CAPRIN1 to decrease the suppression of CAPRIN1 upon S100A11 translation. Then, S100A11 liberated SP3 from nucleolin and promoted SP3 binding to the STAT6 promoter to enhance STAT6 expression and M2a macrophage activation. Macrophage-specific knockdown of S100A11 could alleviate lung inflammation in a CRE-induced murine asthma model in vivo. circS100A11 and S100A11 promote M2a macrophage activation and lung inflammation in asthma model and may serve as potential therapeutic and diagnostic targets in children with asthma.

Type II alveolar epithelial cell aryl hydrocarbon receptor protects against allergic airway inflammation through controlling cell autophagy.

RationaleAryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined.ObjectivesWe sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms.MethodsThe role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f ). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis.Results Sftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen–induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen–induced airway inflammation and, subsequently, allergic asthma.ConclusionThese results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.

Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation.

Allergens have been identified as potential triggers in patients with atopic dermatitis (AD). Patients with AD are highly sensitive to cockroach allergen. The underlying mechanism, however, remains undetermined. Here, we established a cockroach allergen–induced AD-like mouse model, and we demonstrate that repeated exposure to cockroach allergen led to aggravated mouse skin inflammation, characterized by increased type 2 immunity, type 2 innate lymphoid cells (ILC2s), and mast cells. Increased mast cells were also observed in patients with AD. Mast cell–deficient mice (KitW-sh/W-sh) showed diminished skin inflammation, suggesting that mast cells are required in allergen-induced skin inflammation. Furthermore, DC immunoreceptor (DCIR) is upregulated in skin mast cells of patients with AD and mediates allergen binding and uptake. DCIR–/– mice or reconstituted KitW-sh/W-sh mice with DCIR–/– mast cells showed a significant reduction in AD-like inflammation. Both in vitro and in vivo analyses demonstrate that DCIR–/– mast cells had reduced IgE-mediated mast cell activation and passive cutaneous anaphylaxis. Mechanistically, DCIR regulates allergen-induced IgE-mediated mast cell ROS generation and oxidation of calmodulin kinase II (ox-CaMKII). ROS-resistant CaMKII (MM-VVδ) prevents allergen-induced mast cell activation and inflammatory mediator release. Our study reveals a DCIR/ROS/CaMKII axis that controls allergen-induced mast cell activation and AD-like inflammation.

Identification of Per a 13 as a novel allergen in American cockroach

BackgroundCockroaches are an important source of indoor allergens. Environmental exposure to cockroach allergens is closely associated with the development of immunoglobulin E (IgE)-mediated allergic diseases. However, the allergenic components in the American cockroaches are not fully studied yet. In order to develop novel diagnostic and therapeutic strategies for cockroach allergy, it is necessary to comprehensively investigate this undescribed allergen in the American cockroach. MethodsThe full-length cDNA of the potential allergen was isolated from the cDNA library of the American cockroach by PCR cloning. Both the recombinant and natural protein molecules were purified and characterized. The allergenicity was further analyzed by enzyme linked immunosorbent assay, immunoblot, and basophil activation test using sera from cockroach allergic patients. ResultsA novel allergen belonging to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was firstly identified in the American cockroach and named as Per a 13. The cDNA of this allergen is 1255 base pairs in length and contains an open reading frame of 999 base pairs, encoding 332 amino acids. The purified Per a 13 was fully characterized and assessed to react with IgEs from 49.3 % of cockroach allergic patients, and patients with allergic rhinitis were more sensitized to it. Moreover, the allergenicity was further confirmed by immunoblot and basophil activation test. ConclusionsWe firstly identified GAPDH (Per a 13) in the American cockroach, which is a novel type of inhalant allergen derived from animal species. These findings could be useful in developing novel diagnostic and therapeutic strategies for cockroach allergy.

Epithelial Aryl Hydrocarbon Receptor Protects From Mucus Production by Inhibiting ROS-Triggered NLRP3 Inflammasome in Asthma.

BackgroundDespite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.ObjectivesWe sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.MethodsCockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.ResultsCockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.ConclusionsThese results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.

Identification of B cell epitopes of Per a 5 allergen using bioinformatic approach

BackgroundImmune epitopes of allergens are pivotal for development of novel diagnostic and therapeutic modalities. Present study aims to identify antigenic determinants of Per a 5, a clinically relevant cross reactive cockroach allergen. MethodsThe three dimensional structure of Per a 5 was modelled using Modeller 9v11 software. A combination of sequence and structure based computational tools were employed for predicting B cell epitopes. Epitopes were synthesized and immunoreactivity was assessed by ELISA using cockroach hypersensitive patient’s sera. Cross-reactivity potential of predicted epitopes was assessed with SDAP and ConSurf and validated by IgE ELISA with fungal and mite hypersensitive patient’s sera. ResultsPer a 5 structure exhibited good quality factor in ERRAT and high stereochemical stability. In silico analysis revealed six B cell epitopes (BC-P1 to P6). BC-P3 demonstrated significant IgE binding followed by BC-P2 and BC-P1 with cockroach hypersensitive patient’s sera. Per a 5 epitopes demonstrate considerable similarity with broad spectrum of allergens from fungal, mites, helminths, fruits and nuts. Analysis of PD values indicate BC-P4 to be well conserved among dust mite and helminth GSTs (8.89, 10.63 and 10.69 with D. pteronyssinus, W. bancrofti and F. hepatica respectively). ConSurf analysis of Per a 5 revealed specific enrichment of evolutionarily similar amino acid residues in BC-P2 (with fungal and mite GSTs) and BC-P4 (with mite and helminth GSTs). Further, IgE binding analysis of epitopes demonstrate BC-P2, BC-P3 and BC-P5 as high IgE binders in fungal hypersensitive sera while BC-P1, BC-P2, BC-P4 and BC-P5 demonstrated significant IgE binding with mite hypersensitive sera. ConclusionsAmong the predicted epitopes, BC-P3 demonstrates maximal IgE binding ability. Computational analysis suggests strong evolutionary conservation and cross reactive potential of BC-P4 with allergens in dust mite and helminths. ELISA highlights predictive potential of analysing evolutionarily conserved residues for uncovering potentially cross reactive antigenic determinants. General significanceImmune epitopes of Per a 5 were identified for aiding molecular diagnosis and potential cross reactivity.

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.

BackgroundCharacterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen‐specific T cell reactivity in a cohort of CR allergic children with asthma.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild‐to‐moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining.ResultsHighly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL‐4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract.ConclusionsOur results demonstrate that in children with mild‐to‐moderate asthma, CR‐specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

Household determinants of biocontaminant exposures in Canadian homes

Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor. The dust samples were analyzed for house dust mite allergens (Der f 1 and Der p 1), cat allergen (Fel d 1), cockroach allergen (Bla g 1), beta‐(1,3)‐D‐glucan, and endotoxin. Household information was obtained through questionnaires and home inspections. We performed univariate and multivariate analyses to identify household determinants of biocontaminant loadings and mold odor presence. We observed large regional variations for all biocontaminants, except for cockroach allergen. The ranges of the contaminants measured in loadings and concentrations were similar to that of previous Canadian studies. Household characteristics including presence of carpeting, low floor cleaning frequency, older home age, presence of pets, and indoor relative humidity above 45% were positively associated with the presence of multiple indoor biocontaminants. High floor cleaning frequency and use of dehumidifiers were negatively associated with the presence of multiple indoor biocontaminants. Mold odor was positively associated with older home age, past water damage, and visible mold growth.

Patterns of allergic sensitization and factors associated with emergence of sensitization in the rural tropics early in the life course: findings of an Ecuadorian birth cohort.

Introduction: There are limited data on emergence of allergic sensitization (or atopy) during childhood in tropical regions.Methods: We followed a birth cohort of 2,404 newborns to 8 years in tropical Ecuador and collected: risk factor data by maternal questionnaires periodically from birth; atopy was measured by skin prick test reactivity (SPT) to aeroallergens in parents, and aeroallergens and food allergens in children at 2, 3, 5, and 8 years; and stool samples for soil-transmitted helminths (STH) from children periodically to 8 years and from parents and household members at the time of recruitment of cohort children. Data on risk factors were measured either at birth or repeatedly (time-varying) from birth to 8 years. Longitudinal repeated-measures analyses were done using generalized estimating equations to estimate the age-dependent risk of positive SPT (SPT+) to any allergen or mite during early childhood.Results: SPT+ to any allergen was present in 29.0% of fathers and 24.8% of mothers, and in cohort children increased with age, initially to mite but later to cockroach, reaching 14.8% to any allergen (10.7% mite and 5.3% cockroach) at 8 years. Maternal SPT+, particularly presence of polysensitization (OR 2.04, 95% CI 1.49–2.77) significantly increased the risk of SPT+ during childhood, while household overcrowding at birth decreased the risk (OR 0.84, 95% CI 0.72–0.98). For mite sensitization, maternal polysensitization increased (OR 2.14, 95% CI 1.40–3.27) but rural residence (OR 0.69, 95% CI 0.50–0.94) and birth order (3rd−4th vs. 1st−2nd: OR 0.71, 95% CI 0.52–0.98) decreased the risk. Time-varying exposures to agricultural activities (OR 0.77, 95% CI 0.60–0.98) and STH parasites (OR 0.70, 95% CI 0.64–0.91) during childhood decreased while anthelmintics increased the childhood risk (OR 1.47, 95% CI 1.05–2.05) of mite sensitization.Conclusion: Our data show the emergence of allergic sensitization, primarily to mite and cockroach allergens, during childhood in tropical Ecuador. A role for both antenatal and post-natal factors acting as potential determinants of SPT+ emergence was observed.

Intranasal delivery of allergen in a nanoemulsion adjuvant inhibits allergen-specific reactions in mouse models of allergic airway disease.

Atopic diseases are an increasing problem that involve both immediate hypersensitivity reactions mediated by IgE and unique cellular inflammation. Many forms of specific immunotherapy involve the administration of allergen to suppress allergic immune responses but are focused on IgE-mediated reactions. In contrast, the effect of allergen-specific immunotherapy on allergic inflammation is complex, not entirely consistent and not well understood. We have previously demonstrated the ability of allergen administered in a nanoemulsion (NE) mucosal adjuvant to suppress IgE-mediated allergic responses and protect from allergen challenge in murine food allergy models. This activity was associated with decreases in allergen-specific IL-10 and reductions in allergic cytokines and increases in regulatory T cells. Here, we extend these studies to using 2 distinct models, the ovalbumin (OVA) and cockroach (CRA) models of allergic airway disease, which are based predominantly on allergic inflammation. Acute or chronic allergic airway disease was induced in mice using ovalbumin and cockroach allergen models. Mice received three therapeutic immunizations with allergen in NE, and reactivity to airway challenge was determined. Therapeutic immunization with cockroach or OVA allergen in NE markedly reduced pathology after airway challenge. The 2 models demonstrated protection from allergen challenge-induced pathology that was associated with suppression of Th2-polarized immune responses in the lung. In addition, the reduction in ILC2 numbers in the lungs of allergic mice along with reduction in epithelial cell alarmins, IL-25 and IL-33, suggests an overall change in the lung immune environment induced by the NE immunization protocol. These results demonstrate that suppression of allergic airway inflammation and bronchial hyper-reactivity can be achieved using allergen-specific immunotherapy without significant reductions in allergen-specific IgE and suggest that ILC2 cells may be critical targets for this activity.

Aryl hydrocarbon receptor modulates airway inflammation in mice with cockroach allergen-induced asthma by regulating Th17/Treg differentiation

To investigate whether aryl hydrocarbon receptor (AhR) modulates cockroach allergen (CRE)-induced asthma by regulating Th17/Treg differentiation. Mouse models of CRE-induced asthma established by sensitizing and challenging the mice with CRE were randomized into asthma model group, AhR agonist group treated with TCDD (10 μg/ kg), and AhR antagonist group treated with TCDD and CH223191 (10 mg/kg) (n=5), with 5 mice without CRE challenge as the control group. The expressions of AhR, Cyp1a1 and Cyp1b1 mRNA in the lung tissues of the mice were detected using RT-PCR, and pulmonary inflammation was evaluated with immumohistochemical staining. The expressions of inflammatory cytokines in the lungs were detected using ELISA, and the expression of Treg in the lung tissues and pulmonary lymph nodes was analyzed with flow cytometry. Both TCDD and CH223191 were capable of modulating pulmonary expressions of AhR and its downstream genes Cyp1a1 and Cyp1b1 in asthmatic mice (P < 0.002). TCDD treatment significantly decreased inflammatory cells and mucus production in the lungs of asthmatic mice, and BALFs from TCDD-treated mice with CRE challenge contained lowered levels of the proinflammatory factors including IL-4, IL-13 and IL-17A (P < 0.001) but increased anti-inflammatory factors including IL-10, IL-22 and TGF-β1 (P < 0.001). All these changes were significantly reversed by treatment with CH223191 to the levels comparable with those in the asthma model group (P>0.05). More importantly, TCDD treatment significantly increased the number of Tregs cells and FOXP3 expression and lowered RORγt mRNA expression in the lungs and pulmonary lymph nodes in asthmatic mice (P < 0.001); inhibition of AhR with CH223191, as compared with TCDD, significantly decreased the expression of CD4+CD25+Foxp3+Treg cells in the lungs and pulmonary lymph nodes and the expression of FOXP3 mRNA in lymphocytes and increased RORγt mRNA expression (P < 0.001) to the levels comparable with those in asthma model group (P>0.05). AhR activation modulates airway inflammation in mice with CRE-induced asthma by modulating the differentiation of Th17/Treg.

Intestinal helminthic infection and allergic disorders among school children enrolled in mass deworming program, Sululta, Ethiopia

BackgroundIntestinal helminths have been proposed to have a protective role against allergic sensitization and atopic diseases. However, consistent data demonstrating this are lacking in Sub-Saharan countries. We aimed to assess the association between intestinal helminths and allergic disorders among school children enrolled in mass deworming program in Sululta, Ethiopia.MethodsA cross sectional study was conducted among 526 school children aged 5 to 14 years old from primary government schools in Sululta district, Ethiopia. An interviewer-led questionnaire administered to parents provided information on demographic and lifestyle variables. Questions on allergic disease symptoms were collected using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire 6 months following deworming treatments. Atopy was defined as a positive skin prick test reaction to one or both dust mite (Dermatophagoides) and German cockroach (Blatella germanica) allergens. Fresh stool samples were collected, processed, and examined by direct wet mount, Kato-Katz technique, and formol-ether concentration technique. Multivariate logistic regressions were used to assess the association between allergic disorder and helminths infection.ResultsOf the total 526 school children, 58.2% were females. Overall, 24% (126/526) had allergic symptoms, 5.1% (27/526) had atopy, and 16.9% (89/526) had intestinal helminths. There was no association between helminthic infection and self-reported allergic symptoms (P = 0.317), but Ascaris lumbricoides infection was positively associated with atopy (AOR = 4.307, 95% CI 1.143–16.222, P = 0.031). Atopy was related to increased allergy symptoms (AOR = 2.787, 95% CI 1.253–6.197, P = 0.012), and family history of allergy was associated with increased childhood allergy (AOR = 2.753, 95% CI 1.565–4.841, P = 0.001). Deworming in the past 6 months showed a reduced odd of self-reported allergic symptoms (AOR = 0.581, 95% CI 0.366–0.954, P = 0.034).ConclusionWhile no significant association between self-reported allergy and helminths was found in this study, this may have been due to the low prevalence and intensity of helminthic infection in the sample. There was a positive association between Ascaris lumbricoides and atopy. To further examine the underlying mechanism behind this positive association, a longitudinal study is needed.

Associations between Environmental dust composition and Atopic Dermatitis in urban and rural settings.

Environmental exposures are involved in the pathogenesis of the allergic phenotype and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments. To compare house dust composition in urban and rural settings and correlate them with AD outcomes. Dust samples were collected from the beds of 156 children aged 6months to 3years. 42% of participants had atopic dermatitis. Samples were analyzed for bacterial endotoxin, fungal (β-1,3-glucan) levels, and house dust mite, cockroach, dog, cat, mouse, and peanut allergen. Exposures were compared in urban and rural environments and in participants with and without AD. Endotoxin but not fungal β-glucan exposure is higher in the environment of healthy controls than children with AD in both urban and rural settings. House dust mite allergen exposure is high in urban and rural settings with Dermatophagoides detected in 100% of samples. Cat and dog allergen exposure mirrors pet ownership patterns which differ slightly between groups and environments. Mouse allergen exposure is higher in urban homes. Environmental endotoxin may be protective against AD in both urban and rural settings. There are marked differences in allergen exposure in urban and rural settings, but these are unlikely to be important protective or risk factors.

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Removal and Replacement of Endogenous Ligands from Lipid-Bound Proteins and Allergens.

Many major allergens bind to hydrophobic lipid-like molecules, including Mus m 1, Bet v 1, Der p 2, and Fel d 1. These ligands are strongly retained and have the potential to influence the sensitization process either through directly stimulating the immune system or altering the biophysical properties of the allergenic protein. In order to control for these variables, techniques are required for the removal of endogenously bound ligands and, if necessary, replacement with lipids of known composition. The cockroach allergen Bla g 1 encloses a large hydrophobic cavity which binds a heterogeneous mixture of endogenous lipids when purified using traditional techniques. Here, we describe a method through which these lipids are removed using reverse-phase HPLC followed by thermal annealing to yield Bla g 1 in either its Apo-form or reloaded with a user-defined mixture of fatty acid or phospholipid cargoes. Coupling this protocol with biochemical assays reveal that fatty acid cargoes significantly alter the thermostability and proteolytic resistance of Bla g 1, with downstream implications for the rate of T-cell epitope generation and allergenicity. These results highlight the importance of lipid removal/reloading protocols such as the one described herein when studying allergens from both recombinant and natural sources. The protocol is generalizable to other allergen families including lipocalins (Mus m 1), PR-10 (Bet v 1), MD-2 (Der p 2) and Uteroglobin (Fel d 1), providing a valuable tool to study the role of lipids in the allergic response.

IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease.

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort. Ex vivo T cell activation (Ox40/PDL-1 expression) of PBMCs stimulated with peptide pools derived from 11 German cockroach proteins, including nine official cockroach allergens, plus chitinase and vitellogenin, was determined by flow cytometry. IgE prevalences to chitinase (17%) and hemocyanin (44%) were comparable to values for the other eight allergens that we previously reported (21–57%). Hemocyanin (Bla g 3), was a major allergen (one to which more than 50% of patients with an allergy to its source react) for a sub-group of 15 highly cockroach-sensitized subjects (IgE > 3.5 kUA/L: 53%). Chitinase was officially named as new allergen Bla g 12. Cockroach-specific IgE levels in plasma showed excellent correlation with the sum of 10 allergen-specific IgE (r = 0.94, p < 0.001). T cell reactivity to 11 proteins was highly variable among subjects, the highest being for vitellogenin, followed by Bla g 3. The main finding was that cockroach allergen-specific IgE and T cell reactivity patterns were unique per subject, and lacked immunodominant allergens and correlation with clinical phenotype/disease severity in the studied cohort. Knowing the subject-specific B/T cell reactivity profiles to a comprehensive panel of cockroach allergens will contribute to diagnosis of cockroach allergy and will be important for planning and assessing allergen immunotherapy outcomes, according to the allergen content in therapeutic cockroach extracts.

Stability of Cockroach Allergens Versus Non-allergens

Recent statistical evidence suggests that allergens are more stable and more highly expressed than other proteins from an allergen source. These factors may influence human exposure and, on a smaller scale, stability may affect processing by sentinel dendritic cells skewing the immune response toward allergy. Interestingly, for cockroach allergens purified from frass, the allergen stabilities were not statistically greater than their non-allergen counterparts, likely due to the high mean stability of the latter.