Burgers, Fast Foods, and Increased Associated Risk for Atopic Dermatitis: A Cross-Sectional Study of Dietary Habits among Young Chinese Adults in Singapore/Malaysia.

BACKGROUND: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. METHODS: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. RESULTS: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719-0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714-0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606-0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. CONCLUSION: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.

Diving deep into fish allergen immunotherapy: Current knowledge and future directions.

Fish allergy is one of the "big nine" categories of food allergens worldwide, and its prevalence is increasing with the higher demand for this nutritious food source. Fish allergies are a significant health concern as it is a leading cause of food anaphylaxis, accounting for 9% of all deaths from anaphylaxis. The gaps in treating fish allergies at present are the incomplete identification of fish allergens, lack of component-resolved diagnosis of fish allergens in the clinical setting, and the variability in sensitization profiles based on different fish consumption practices. Allergen immunotherapy (AIT) improves tolerance towards accidental consumption of fish and is longer lasting than pharmacotherapy. Current practice or research of fish AIT ranges from the use of whole fish via oral desensitization, to the use of purified recombinant parvalbumin and its hypoallergenic variant, passive IgG immunization, and modifying the allergenicity of parvalbumin by changing the diet of farmed fish. However, the focus of fish allergen-based studies in the context of AIT has been restricted to parvalbumins. More research is required to understand the involvement of other fish allergens, and several other strategies of AIT including peptide vaccines, DNA vaccines, hybrid allergens, and the use of nanobodies that have the capacity to treat multiple allergens have been proposed. For AIT, other important aspects to consider are the route of desensitization, and the biomarkers to assess the success of immunotherapy. Finally, we also address several clinical considerations for fish AIT.

A Dietary Pattern for High Estimated Total Fat Amount Is Associated with Enhanced Allergy Sensitization and Atopic Diseases among Singapore/Malaysia Young Chinese Adults.

INTRODUCTION: Frequent dietary patterns for fast food diets are suggested to be a risk factor for atopic disease development. Excessive dietary fats in fast foods are postulated to promote low-grade chronic inflammation. However, no studies in Asia have yet to characterize the dietary pattern for high-fat foods with atopic diseases. Thus, this study aims to assess the association between dietary fats with the prevalence of atopic diseases in an allergic cohort. METHODS: Through an investigator-administered questionnaire that follows the International Study of Asthma and Allergies in Childhood (ISAAC) protocol, we evaluated the eating habits, lifestyle behaviours, sociodemographics, and atopic symptoms, and history among 11,494 young Chinese adults in Singapore and Malaysia. A skin prick test (SPT) for common house dust mites was also conducted to determine the atopic (allergic) status. We identified 1,550 atopic dermatitis (AD), 1,301 allergic asthma (AS), and 3,757 allergic rhinitis (AR) atopic cases. We derived a novel dietary index, Diet Quality based on Total Fat Amount (DQTFA), to examine the association between eating patterns for estimated total fat amount with various atopic outcomes. RESULTS: There was a preponderance of subjects having positive SPT reaction (69.0%) with the prevalence of AR being the highest (32.7%), then AD (13.5%), and AS (11.3%). Additionally, there is a significantly higher proportion of subjects with an atopy background and atopic diseases consume diets with a high estimated mean fat amount. The adherence to a dietary pattern of the higher estimated total fat amount was shown to be strongly associated with all atopic diseases and exhibited dose-dependent responses in the univariate analysis. These associations remained significant even with the adjustments for age, gender, body mass index, use of alcohol, sedentary lifestyles, and physical activity. A dietary pattern for high-fat amount is more strongly associated with AS (adjusted odds ratio [AOR]: 1.524; 95% confidence interval [CI]: 1.216-1.725; p < 0.001) and AR (AOR: 1.294; 95% CI: 1.107-1.512; p < 0.001) compared to AD (AOR: 1.278; 95% CI: 1.049-1.559; p < 0.05). Finally, it was shown that having either one of the atopic comorbidities was strongly associated with a dietary pattern of high-fat amounts (AOR: 1.360; 95% CI: 1.161-1.594; p < 0.001). CONCLUSION: Our findings altogether provide initial evidence that the dietary pattern of a diet high in fat amount is associated with an increased risk of atopy and atopic diseases in young Chinese adults in Singapore and Malaysia. Balancing the consumption of dietary fats and changing personal dietary habits by choosing foods of the lower fat amount may reduce the associated odds of atopic diseases.

The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma.

INTRODUCTION: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. RESULTS: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele "G" identified as protective against the disease (adjusted logistic p = 6.56 × 10-9, OR = 0.625, 95% CI: 0.544-0.718). The allele "G" of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype "GG" of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. CONCLUSIONS: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.

A dietary pattern of frequent plant-based foods intake reduced the associated risks for atopic dermatitis exacerbation: Insights from the Singapore/Malaysia cross-sectional genetics epidemiology cohort.

BACKGROUND: The prevalence of atopic dermatitis (AD) has been increasing in recent years, especially in Asia. There is growing evidence to suggest the importance of dietary patterns in the development and management of AD. Here, we seek to understand how certain dietary patterns in a Singapore/Malaysia population are associated with various risks of AD development and exacerbation. METHODS: A standardized questionnaire following the International Study of Asthma and Allergies in Childhood (ISAAC) guidelines was investigator-administered to a clinically and epidemiology well-defined allergic cohort of 13,561 young Chinese adults aged 19-22. Information on their sociodemographic, lifestyle, dietary habits, and personal and family medical atopic histories were obtained. Allergic sensitization was assessed by a skin prick test to mite allergens. Spearman's rank-order correlation was used to assess the correlation between the intake frequencies of 16 food types. Dietary patterns were identified using principal component analysis. Four corresponding dietary scores were derived to examine the association of identified dietary patterns with allergic sensitization and AD exacerbations through a multivariable logistic regression that controlled for age, gender, parental eczema, BMI, and lifestyle factors. RESULTS: The correlation is the strongest between the intake of butter and margarine (R = 0.65). We identified four dietary patterns, "high-calorie foods", "plant-based foods", "meat and rice", and "probiotics, milk and eggs", and these accounted for 47.4% of the variance in the dietary habits among the subjects. Among these patterns, moderate-to-high intake of "plant-based foods" conferred a negative association for chronic (Adjusted odds ratio (AOR): 0.706; 95% confidence interval (CI): 0.589-0.847; p < 0.001) and moderate-to-severe AD (AOR: 0.756; 95% CI: 0.638-0.897; p < 0.01). "Meat and rice" and "probiotics, milk and eggs" were not significantly associated with AD exacerbation. While frequent adherence to "high-calorie foods" increased the associated risks for ever AD and moderate-to-severe AD, having a higher adherence to "plant-based foods" diminished the overall associated risks. CONCLUSIONS: Frequent adherence to "plant-based foods" was associated with reduced risks for AD exacerbation in young Chinese adults from Singapore/Malaysia. This provides the initial evidence to support the association between dietary factors and AD. Further research is needed to better understand the pathomechanisms underlying diet and AD exacerbations.

Golgin A7 family member B (GOLGA7B) is a plausible novel gene associating high glycaemic index diet with acne vulgaris.

While the IGF1/FoxO1/mTORC1 signalling pathway is a well-established nutrigenomic link between high glycaemic index (GI)/glycaemic load (GL) diet and acne vulgaris, other signalling pathways remain elusive. Therefore, we aimed to investigate other genes that are involved in the high GI/GL diet-acne link, using our Singapore/Malaysia population epidemiological, genomics and transcriptomics data. High GI/GL dietary habit of 3207 acne cases (1869 and 1341 further classified into severity and scarring grades, respectively) and 2521 controls were evaluated based on Quality of Diet based on Glycaemic Index Score (QDGIS). Overlapping concordant differentially expressed genes (DEGs) between acne case-controls and QDGIS poor-moderate/good classes were identified from whole-transcriptome sequencing data of PBMC of a subset of participants. Finally, we assessed the expression quantitative trait loci (eQTL) association of single nucleotide polymorphisms (SNPs) of the concordant DEGs. Daily intake of fruits significantly reduced the risk of acne presentation, severity and scarring by up to 48.5%. Those with good QDGIS had significantly lower risk of mild and moderate/severe acne, and grade 1/2 acne scarring. Sequential filtering identified four overlapping concordant DEGs that were significantly associated with acne and QDGIS, namely GOLGA7B, SNCB, LOC102723849 and LOC283683. Combining transcriptome and genetic association data, we identified intronic SNP rs1953947 in GOLGA7B as an eQTL for acne. In conclusion, we identified GOLGA7B as a plausible novel gene that links high GI/GL with acne, and hence propose a model for the involvement of Golga7b in high GI/GL diet-acne pathogenesis, which includes palmitoyl acyltransferase zDHHC5, fatty acid translocase CD36 and palmitic acid.

Modifiable and non-modifiable epidemiological risk factors for acne, acne severity and acne scarring among Malaysian Chinese: a cross-sectional study.

BACKGROUND: Acne vulgaris, a highly prevalent multifactorial inflammatory skin disease, can be categorised into different severity and scarring grades based on the type, number, and severity of lesions. While many epidemiology studies have investigated the risk factors for acne presentation, fewer studies have specifically studied the risk factors for acne severity and scarring. Therefore, this study investigated the prevalence of acne, acne severity and scarring grades, and their associated non-modifiable and modifiable epidemiological risk factors among Malaysian Chinese. METHODS: A total of 1840 subjects (1117 cases/723 controls) completed an investigator-administered questionnaire as part of a cross-sectional study, which include socio-demographics, familial history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 1051) and scarring (n = 1052) grades by a trained personnel. RESULTS: Majority of the acne cases (up to 69%) had mild acne or Grade 1/2 scarring, while 21.6% had moderate/severe acne and 5.5% had Grade 3/4 scarring. Males had significantly higher risk of presenting with higher grades of acne scarring. Those who had acne, regardless of severity and scarring grades, had strong positive familial history (either in parents and/or sibling). Frequent consumption (most or all days) of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) decreased the risk for acne presentation and higher acne scarring, while periodic consumption (once/twice per week) of nuts and burgers/fast food decreased the risk for higher acne severity. Alcohol drinking was significantly associated with increased risk for acne presentation, while paternal, parental and household smoking were associated with reduced risk of more severe acne. CONCLUSIONS: In conclusion, positive familial history is a strong predisposing factor in influencing acne presentation, severity and scarring. Frequent consumption of foods that are commonly consumed during breakfast is protective against acne presentation.

Sensitization to Airborne Fungal Allergens Associates with Asthma and Allergic Rhinitis Presentation and Severity in the Singaporean/Malaysian Population.

Fungal spores and conidia are the major components of total airspora in the tropical Asia environment, and their sensitization patterns are often associated with allergic diseases such as asthma, allergic rhinitis (AR), and atopic dermatitis. Hence, we recruited a cross-sectional cohort of 9223 Singapore/Malaysia Chinese adults and assessed their sensitization against Curvularia lunata allergen using the skin prick test approach. A subset of this cohort (n = 254) was also screened for specific Immunoglobulin E (sIgE) titers against a panel of 11 fungal allergens. We found significant association of Curvularia lunata sensitization with the risk of asthma (OR = 1.66, 95% CI: 1.17-2.33; p = 0.00391) and AR (OR = 1.69, 95% CI: 1.18-2.41; p = 0.00396). Among asthmatic patients (n = 1680), Curvularia lunata sensitization also increased frequencies of wheezing symptoms (OR = 1.81, 95% CI: 1.05-2.96; p = 0.0239), general practitioner/specialist visits (OR = 2.37, 95% CI: 1.13-4.61; p = 0.0157), and other asthma-related exacerbation events (OR = 2.14, 95% CI: 1.04-4.10; p = 0.0289). In our serum cohort, sensitization to Aspergillus spp. was the most common fungal sensitization, with 23.6% (n = 60) had a class 3 and above sensitization (positive sensitization; sIgE titers of > 3.5 kU/L) against this allergen. Increasing sIgE titer against Aspergillus spp. was also correlated with increased AR risk and AR-related symptoms. In conclusion, our findings emphasize an important role of fungal sensitization in the manifestations of asthma and AR in the Southeast Asian Chinese population.

Revisiting the Timing of Action of the PAG Adaptor Using Quantitative Proteomics Analysis of Primary T Cells.

The protein tyrosine kinase LCK plays a key role in TCR signaling, and its activity is dynamically controlled by the tyrosine kinase C-terminal Src kinase (CSK) and the tyrosine phosphatase CD45. CSK is brought in contiguity to LCK via binding to a transmembrane adaptor known as phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG). The lack of a blatant phenotype in PAG-deficient mice has impeded our understanding of the mechanisms through which PAG exerts its negative-regulatory role in TCR signaling. We used quantitative mass spectrometry and both thymocytes and CD4(+) T cells from mice in which a tag for affinity purification was knocked in the gene coding for PAG to determine the composition and dynamics of the multiprotein complexes that are found around PAG over 5 min of activation. Most of the high-confidence interactions that we observed were previously unknown. Using phosphoproteomic analysis, PAG showed low levels of tyrosine phosphorylation in resting primary mouse CD4(+) T cells; the levels of tyrosine phosphorylation increased and reached a maximum 2 min after stimulation. Analysis of the dynamics of association of the protein tyrosine phosphatase PTPN22 and lipid phosphatase SHIP-1 with PAG following T cell activation suggests that both cooperate with CSK to terminate T cell activation. Our findings provide a model of the role for PAG in mouse primary CD4(+) T cells that is consistent with recent phosphoproteomic studies of the Jurkat T cell line but difficult to reconcile with former biochemical studies indicating that PAG is constitutively phosphorylated in resting T cells and rapidly dephosphorylated once the TCR is engaged.

Atopic dermatitis-associated genetic variants regulate LOC100294145 expression implicating interleukin-27 production and type 1 interferon signaling.

Background: Atopic dermatitis (AD) is a complex inflammatory disease with a strong genetic component. A singular approach of genome wide association studies (GWAS) can identify AD-associated genetic variants, but is unable to explain their functional relevance in AD. This study aims to characterize AD-associated genetic variants and elucidate the mechanisms leading to AD through a multi-omics approach. Methods: GWAS identified an association between genetic variants at 6p21.32 locus and AD. Genotypes of 6p21.32 locus variants were evaluated against LOC100294145 expression in peripheral blood mononuclear cells (PBMCs). Their influence on LOC100294145 promoter activity was measured in vitro via a dual-luciferase assay. The function of LOC100294145 was then elucidated through a combination of co-expression analyses and gene enrichment with g:Profiler. Mendelian randomization was further used to assess the causal regulatory effect of LOC100294145 on its co-expressed genes. Results: Minor alleles of rs116160149 and rs115388857 at 6p21.32 locus were associated with increased AD risk (p = 2.175 × 10-8, OR = 1.552; p = 2.805 × 10-9, OR = 1.55) and higher LOC100294145 expression in PBMCs (adjusted p = 0.182; 8.267 × 10-12). LOC100294145 expression was also found to be increased in those with AD (adjusted p = 3.653 × 10-2). The genotype effect of 6p21.32 locus on LOC100294145 promoter activity was further validated in vitro. Co-expression analyses predicted LOC100294145 protein's involvement in interleukin-27 and type 1 interferon signaling, which was further substantiated through mendelian randomization. Conclusion: Genetic variants at 6p21.32 locus increase AD susceptibility through raising LOC100294145 expression. A multi-omics approach enabled the deduction of its pathogenesis model comprising dysregulation of hub genes involved in type 1 interferon and interleukin 27 signaling.

Sensitization to oil palm pollen associates with risks and severity of allergic diseases.

Background: Elaeis guineensis (Ela g, oil palm) pollen is one of the most predominant species of inhalant allergens in the tropical Southeast Asia region; however, its association with the manifestation of allergic diseases remains largely unexplored. This study aimed to determine the sensitization pattern of oil palm pollen and associate this with the risk and severity of allergic diseases. Methods: Participants were recruited as a part of the Singapore and Malaysia cross-sectional genetic and epidemiological study (SMCSGES). Two independent cohorts were recruited: n = 564 serum samples were collected and serological assessment was performed against a panel of 16 crude inhalant allergens including house dust mite, pet, insect, pollen, and fungal allergens; n = 13 652 Singapore/Malaysia Chinese young adults were recruited and skin prick test was used to assess oil palm sensitization, which was tested for its association with the risk and severity of asthma, allergic rhinitis (AR), and atopic dermatitis (AD). Results: The sensitization rate of oil palm pollen is 9.6% in the n = 564 Singapore/Malaysia cohort. In the n = 13 652 Singapore/Malaysia Chinese cohort, oil palm sensitization significantly associates with increased risks of asthma (p = 1.34x10-4), AR (p = 2.91x10-13), and AD (p = 6.95x10-7). Asthmatic patients with oil palm sensitization have increased risks of wheezing (p = 0.00995), nocturnal cough (p = 0.0122), and exacerbations (p = 0.00139) in the past 12 months. AR patients with oil palm sensitization also have an increased risk of developing moderate-to-severe symptoms (p = 0.00113). Conclusions: We have identified significant associations of oil palm sensitization with increased risks, exacerbations, and the severity of symptoms of allergic diseases in the tropical Southeast Asian region (Singapore/Malaysia).

Different modes of IgE binding to CD23 revealed with major birch allergen, Bet v 1-specific monoclonal IgE.

We investigated the binding of IgE and different types of allergen-IgE complexes to CD23-expressing human B cells. We performed the experiments using chimeric Bip 1 (CB1), a chimeric humanized IgE specific for the major birch allergen, Bet v 1, together with monomeric and oligomeric forms of recombinant Bet v 1 (rBet v 1), and Bet v 1-specific IgG antibodies. In this model IgE binding to CD23 was independent of variations in antibody affinities towards monomeric and oligomeric Bet v 1 as demonstrated by plasmon surface resonance. CB1 alone or in the form of small immune complexes consisting of one molecule of CB1 plus allergen, showed comparable binding to CD23 on B cells. Using anti-IgE antibody probes discriminating CD23-bound from CD23-unbound IgE, it is demonstrated that in large immune complexes obtained with oligomeric Bet v 1 or by super-crosslinking of small immune complexes with Bet v 1-specific IgG, anti-IgE staining of B cells increased. This increase of staining was due to the presence of IgE antibodies in the immune complexes that were not directly engaged in CD23 binding, and thus available for IgE detection. Our study thus reveals that CD23 can bind in a comparable manner to free IgE and IgE-allergen complexes of different size and composition, which may also include allergen-specific IgG. The interplay of free IgE with IgE-allergen immune complexes of different sizes and composition with CD23 binding represents a mechanism for the modulation of CD23-mediated immune responses such as IgE-facilitated allergen presentation in allergic diseases.

Current practices and future trends in cockroach allergen immunotherapy.

PURPOSE OF REVIEW: This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects. SUMMARY: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.

Dual-action potential of cationic cryptides against infections and cancers.

Cryptides are a subfamily of bioactive peptides embedded latently in their parent proteins and have multiple biological functions. Cationic cryptides could be used as modern drugs in both infectious diseases and cancers because their mechanism of action is less likely to be affected by genetic mutations in the treated cells, therefore addressing a current unmet need in these two areas of medicine. In this review, we present the current understanding of cryptides, methods to mine them sustainably using available online databases and prediction tools, with a particular focus on their antimicrobial and anticancer potential, and their potential applicability in a clinical setting.

Dietary Protein Intake and Associated Risks for Atopic Dermatitis, Intrinsic Eczema, and Allergic Sensitization among Young Chinese Adults in Singapore/Malaysia: Key Findings from a Cross-sectional Study.

Through an investigator-administered questionnaire that follows the standard protocol of the International Study of Allergy and Asthma in Childhood, data on symptomatic histories of eczema and dietary habits were collected from 11,494 young Chinese adults in Singapore/Malaysia. Allergic sensitization status was assessed through a skin prick test reactivity to common house dust mites. Using three dietary indices (dietary protein score, animal protein score, and plant protein score), the associations between atopic dermatitis, intrinsic eczema, allergic sensitization, and intake of various proteins were estimated. On average, most subjects frequently eat meat, vegetables, and rice in their diets. Through a multivariable logistic regression adjusted for age, sex, body mass index, and parental eczema, subjects with high dietary protein score (adjusted OR = 1.397; 95% confidence interval = 1.133-1.724; P < 0.003) and high animal protein score (adjusted OR = 1.353; 95% confidence interval = 1.106-1.682; P < 0.003) were associated with increased risk of atopic dermatitis. Interestingly, synergy factor analysis revealed that a higher intake of plant proteins than animal proteins in diets significantly reduced overall associated risks of atopic dermatitis and allergic sensitization but not those of intrinsic eczema. Most importantly, these associations are independent of dietary fat intake. Taken together, frequent adherence to diets rich in plant proteins reduced associated risks of atopic dermatitis in Singapore/Malaysia Chinese adults.

Novel cationic cryptides in Penaeus vannamei demonstrate antimicrobial and anti-cancer activities.

Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.

Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular immune responses.

BACKGROUND: Staphylococcus aureus superinfections occur in more than 90% of patients with atopic dermatitis (AD) and aggravate skin inflammation. S aureus toxins lead to tissue damage and augment T-cell-mediated skin inflammation by a superantigen effect. OBJECTIVE: To characterize IgE-reactive proteins from S aureus. METHODS: A genomic S aureus library was screened with IgE from patients with AD for DNA clones coding for IgE-reactive antigens. One was identified as fibronectin-binding protein (FBP). Recombinant FBP was expressed in Escherichia coli, purified, and tested for specific IgE reactivity in patients with AD. Its allergenic activity was studied in basophil activation experiments and T-cell cultures. The in vivo allergenic activity was investigated by sensitizing mice. RESULTS: Using IgE from patients with AD for screening of a genomic S aureus library, an IgE-reactive DNA clone was isolated that coded for FBP. Recombinant FBP was expressed in E coli and purified. It reacted specifically with IgE from patients with AD and exhibited allergenic activity in basophil degranulation assays. FBP showed specific T-cell reactivity requiring antigen presentation and induced the secretion of proinflammatory cytokines from PBMCs. Mice sensitized with FBP mounted FBP-specific IgE responses, showed FBP-specific basophil degranulation as well as FBP-specific T-cell proliferation, and mixed T(h)2/T(h)1 cytokine secretion. CONCLUSION: Evidence is provided that specific humoral and cellular immune responses to S aureus antigens dependent on antigen presentation represent a novel mechanism for S aureus-induced skin inflammation in AD. Furthermore, FBP may be used for the development of novel diagnostic and therapeutic strategies for S aureus infections.

Allergic rhinitis in Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort: Prevalence, patterns, and epidemiology of allergic rhinitis.

Background: Allergic rhinitis (AR) is characterized by the occurrence of at least 2 symptoms of nasal itching, nasal blockage, rhinorrhea, and sneezing, when not afflicted with a cold or flu, with defined atopic sensitization demonstrated by skin prick test or specific IgE responses. Besides the detriment to standard of living and economic burden of AR, both multicentre and single-cohort studies have observed an increase in AR prevalence in Asia over time. Methods: In total, 12 872 individuals, with mean age 22.1 years (SD = 4.8), were recruited from universities in Singapore and Malaysia. Each participant provided epidemiological data based on an investigator-administered questionnaire adapted from the validated International Study of Allergies and Asthma in Childhood (ISAAC) protocol, and atopy status was determined using a skin prick test (SPT) performed by qualified staff. AR was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and a positive SPT result. Results: Sensitization (determined by SPT) to either Blomia tropicalis or Dermatophagoides pteronyssinus was prevalent in 66.5% of the cohort. Current rhinitis (manifesting ≥2 rhinitis symptoms, within the past 12 months) was observed in 48.9% of our population, while AR, which included atopy status, was estimated at 39.4%. Sneezing and rhinorrhea were the most common symptoms among AR cases. AR prevalence decreased with increasing age (OR: 0.979; 95% CI: 0.969-0.989), while male gender (OR: 2.053; 95% CI: 1.839-2.294), and a parental history of allergic diseases (OR: 2.750; 95% CI: 2.284-3.316) were significant risk factors for AR. Upon adjustment for age, gender, and parental history, housing type (OR: 0.632; 95% CI: 0.543-0.736) and income level (>$6000 vs <$2000; OR: 2.461; 95% CI: 2.058-2.947) remained as significant risk factors for AR, while ever having kept a pet (OR: 1.167; 95% CI: 1.025-1.328) emerged as a risk factor. Conflicting results were obtained for indicators of sedentary lifestyle: frequent physical activity (OR: 1.394; 95% CI: 1.150-1.694) and increased duration spent using the TV/computer (OR: 1.224; 95% CI: 1.006-1.489) both increased the risk of AR. Lastly, we used the Quality of Diet based on Glycaemic Index Score (QDGIS) to assess the Glycaemic Index (GI) level of overall diet. We identified lower GI level of overall diet as a protective factor against AR manifestation (OR: 0.682; 95% CI: 0.577-0.807). Conclusion: While the previously established non-modifiable risk factors for AR were present in our study population, the identification of modifiable risk factors, such as TV/computer usage, and dietary habits, opens a new area for research, both in the areas of gene-environment interaction, and management of AR.

An update on the prevalence, chronicity, and severity of atopic dermatitis and the associated epidemiological risk factors in the Singapore/Malaysia Chinese young adult population: A detailed description of the Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort.

Background: Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD. Methods: There are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation. Results: The prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk. Conclusions: These findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.

Mite component-specific IgE repertoire and phenotypes of allergic disease in childhood: the tropical perspective.

Sensitization to perennial aeroallergens correlates with the risk of persistent asthma (AS) in children. In tropical Singapore, multiple codominant species of mites abound in the indoor environment, and preferential species-specific sensitization has been associated with different phenotypes of allergic disease. We investigated the pattern of mite component-specific IgE (mcsIgE) in children with different phenotypes of clinical allergic disease in an environment with multiple mite species exposure. A prospective evaluation of newly diagnosed patients with clinical diagnosis of allergic rhinitis (AR), atopic dermatitis (AD), or AS and sensitization to one or more aeroallergens were performed. Sera were tested for specific IgE against an extensive panel of Dermatophagoides pteronyssinus and Blomia tropicalis allergens. A total of 253 children were included, mean age 7.3 yr, 79% fulfilled criteria for AR, 46% AS, 71% AD, and 31% for all three. Sensitization to one or both mites was observed in 91% of children, 89% were sensitized to D. pteronyssinus, and 70% to B. tropicalis. The most common mite allergens recognized by these atopic children were Der p 1 (64%), Der p 2 (71%), Blo t 5 (45%), Blo t 7 (44%), and Blo t 21 (56%). Specific IgE responses to an increased number of distinct mite allergens correlated with the complexity of the allergic phenotype. In multivariate analysis, an increased risk for the multi-systemic phenotype (AR + AS + AD) was associated with sensitization to an increased repertoire of mite components (three or more) (OR 4.3, 95% CI 2.1-8.8, p = 0.001) and a positive parental history of AS (OR 2.4, 95% CI 1.2-2.9, p = 0.013). A highly pleiomorphic IgE response to the prevalent indoor mites is associated with the presence of a multi-systemic allergic phenotype in childhood in a tropical environment.