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Fulltext Conformational IgE Epitope Mapping of Der p 2 and the Evaluations of Two Candidate Hypoallergens for Immunotherapy

Reginald K, Chew FT

Sci Rep, 2018 02 21;8(1):3391.
PMID: 29467434 DOI: 10.1038/s41598-018-21792-1

Epitope mapping of Der p 2, a clinically important dust-mite allergen is the first step in designing immunotherapy hypoallergen vaccine candidates. Twenty-one single alanine mutants of Der p 2 were generated and their secondary structure was analysed using circular dichroism spectra. Only one mutant, K96A resulted in a misfolded protein. All mutants were tested for serum IgE reactivity using serum from dust mite allergic individuals by immuno dot-blots. Mutations to five residues, N10, E25, K77, K96 and E102 consistently showed reduced IgE reactions compared to wild-type Der p 2, and therefore these residues constitute the major IgE epitopes of Der p 2. Two mutants with consistent low IgE binding, K96A and E102A, were subsequently evaluated as hypoallergen candidates. IgG antibodies raised in mice against both mutants could inhibit human IgE-binding to WT Der p 2. Both mutants had intact T-cell epitopes as they were able to stimulate peripheral blood mononuclear cell proliferation similar to WT Der p 2. However, a switch in Th1:Th2 cytokine profile was not observed. In summary, we have identified the major conformational epitopes of Der p 2, and evaluated two Der p 2 hypoallergen vaccine candidates for immunotherapy.
Fulltext The major allergen Der p 2 is a cholesterol binding protein

Reginald K, Chew FT

Sci Rep, 2019 02 07;9(1):1556.
PMID: 30733527 DOI: 10.1038/s41598-018-38313-9

Der p 2 is a major dust mite allergen and >80% of mite allergic individuals have specific IgE to this allergen. Although it is well characterized in terms of allergenicity, there is still some ambiguity in terms of its biological function. Three-dimensional structural analysis of Der p 2 and its close homologues indicate the presence of a hydrophobic cavity which can potentially bind to lipid molecules. In this study, we aimed to identify the potential ligand of Der p 2. Using a liposome pulldown assay, we show that recombinant Der p 2 binds to liposomes prepared with exogenous cholesterol in a dose dependent fashion. Next, an ELISA based assay using immobilized lipids was used to study binding specificities of other lipid molecules. Cholesterol was the preferred ligand of Der p 2 among 11 different lipids tested. Two homologues of Der p 2, Der f 2 and Der f 22 also bound to cholesterol. Further, using liquid chromatography-mass spectrometry (LC-MS), we confirmed that cholesterol is the natural ligand of Der p 2. Three amino acid residues of Der p 2, V104, V106 and V110 are possible cholesterol binding sites, as alanine mutations of these residues showed a significant decrease in binding (p
Fulltext Current practices and future trends in cockroach allergen immunotherapy

Reginald K, Chew FT

Mol Immunol, 2023 Sep;161:11-24.
PMID: 37480600 DOI: 10.1016/j.molimm.2023.07.004

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.
Fulltext Blo t 2: Group 2 allergen from the dust mite Blomia tropicalis

Reginald K, Pang SL, Chew FT

Sci Rep, 2019 Aug 22;9(1):12239.
PMID: 31439916 DOI: 10.1038/s41598-019-48688-y

Blomia tropicalis has been recognized as a cause of allergic diseases in the tropical and subtropical regions. Here we report the immuno-characterization of its group 2 allergen, Blo t 2. Allergen Blo t 2 was amplified from the cDNA of B. tropicalis using degenerate primers, expressed in Escherichia coli as a recombinant protein and purified to homogeneity. The mature protein of Blo t 2 was 126 amino acids long with 52% sequence identity to Der p 2 and apparent molecular mass of 15 kDa. Circular dichroism spectroscopy showed that Blo t 2 is mainly a beta-sheeted protein. We confirmed the presence of three disulfide bonds in recombinant (r) Blo t 2 protein using electrospray mass spectrometry. Thirty-four percent of dust-mite allergic individuals from the Singapore showed specific IgE binding to rBlo t 2 as tested using immuno dot-blots. IgE-cross reactivity assays showed that Blo t 2 had between 20-50% of unique IgE-epitopes compared to Der p 2. IgE binding of native and recombinant forms of Blo t 2 were highly concordant (r2 = 0.77, p
Fulltext Development of Peptide Vaccines in Dengue

Reginald K, Chan Y, Plebanski M, Poh CL

Curr Pharm Des, 2018;24(11):1157-1173.
PMID: 28914200 DOI: 10.2174/1381612823666170913163904

Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed.
Diving deep into fish allergen immunotherapy: Current knowledge and future directions

Reginald K, Nadeem K, Yap EZY, Latiff AHA

Asian Pac J Allergy Immunol, 2024 Mar;42(1):1-13.
PMID: 38165149 DOI: 10.12932/AP-030923-1687

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

Abd El-Aal AAA, Jayakumar FA, Reginald K

Drug Discov Today, 2023 Nov;28(11):103764.
PMID: 37689179 DOI: 10.1016/j.drudis.2023.103764

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.
Fulltext Characterization of Der f 22 - a paralogue of the major allergen Der f 2

Reginald K, Tan CL, Chen S, Yuen L, Goh SY, Chew FT

Sci Rep, 2018 08 06;8(1):11743.
PMID: 30082894 DOI: 10.1038/s41598-018-30224-z

We previously identified an expressed sequence tag clone, Der f 22, showing 41% amino acid identity to published Der f 2, and show that both genes are possible paralogues. The objective of this study was to characterize the genomic, proteomic and immunological functions Der f 22 and Der f 2. The full-length sequence of Der f 2 and Der f 22 coded for mature proteins of 129 and 135 amino acids respectively, both containing 6 cysteine residues. Phylogenetic analysis of known group 2 allergens and their homologues from our expressed sequence tag library showed that Der f 22 is a paralogue of Der f 2. Both Der f 2 and Der f 22 were single gene products with one intron. Both allergens showed specific IgE-binding to over 40% of the atopic patients, with limited of cross-reactivity. Both allergens were detected at the gut region of D. farinae by immunostaining. Der f 22 is an important allergen with significant IgE reactivity among the atopic population, and should be considered in the diagnostic panel and evaluated as future hypoallergen vaccine therapeutic target.
Investigating immune responses of the house cricket, Acheta domesticus to pathogenic Escherichia coli K1

Reginald K, Wong YR, Shah SMR, Teh KF, Freddy Jalin EJ, Khan NA

Microbes Infect, 2021 07 28;23(9-10):104876.
PMID: 34332091 DOI: 10.1016/j.micinf.2021.104876

BACKGROUND: Insects models are excellent models of the innate immune system, as they are free from the influences of vertebrate adaptive immunity. Crickets are hemimetabolous insects belonging to the order Orthopteran order that have not been as extensively characterized as other holometabolous insects, and may provide new insights into the insect immune responses. In this study, we aim to characterize the innate immune responses of the common house cricket, Acheta domesticus in response to a human pathogenic bacterium E. coli K1.
METHODS: Crickets were injected with sterile buffer, live E. coli K1 or heat-killed E. coli K1. Physiological effects such as mortality and weight change of the crickets were determined 24-, 48- and 72-h post injection while immunological effects such as hemocyte counts, bacteremia, phenoloxidase and lysozyme activity of the crickets were measured at 2- and 24-h post-injection.
RESULTS: The injection of E. coli K1 in crickets resulted in >85% mortality 3-days post injection, accompanied by significant weight loss. E. coli K1 injection caused a significant increase in both phenoloxidase and lysozyme activities in cricket hemolymphs 24-h post injection. Live E. coli K1 injected crickets resulted in a significant reduction in circulating hemocytes 24-h post injection which was not observed in other treatment groups. This was consistent with the resolution of bacteremia observed 24-h post infection in live E. coli K1 injected crickets.
CONCLUSION: Our study provides new insights on the innate immune response to pathogenic E. coli K1 in a cricket model.
Fulltext A Dietary Pattern for High Estimated Total Fat Amount Is Associated with Enhanced Allergy Sensitization and Atopic Diseases among Singapore/Malaysia Young Chinese Adults

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

Int Arch Allergy Immunol, 2023;184(10):975-984.
PMID: 37393903 DOI: 10.1159/000530948

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

Abd El-Aal AAA, Jayakumar FA, Lahiri C, Tan KO, Reginald K

Sci Rep, 2023 Sep 06;13(1):14673.
PMID: 37673929 DOI: 10.1038/s41598-023-41581-9

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.
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

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

JID Innov, 2023 Nov;3(6):100224.
PMID: 37731471 DOI: 10.1016/j.xjidi.2023.100224

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.
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

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

BMC Public Health, 2023 Sep 19;23(1):1818.
PMID: 37726698 DOI: 10.1186/s12889-023-16736-y

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

Teo WY, Lim YYE, Sio YY, Say YH, Reginald K, Chew FT

World Allergy Organ J, 2024 Feb;17(2):100869.
PMID: 38298829 DOI: 10.1016/j.waojou.2023.100869

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.
Fulltext Functional Polymorphisms Regulate FOXO1 Transcript Expression and Contribute to the Risk and Symptom Severity of HDM-Induced Allergic Rhinitis

Sio YY, Du K, Lam TYW, Say YH, Reginald K, Chew FT

Int Arch Allergy Immunol, 2025;186(1):1-11.
PMID: 39208774 DOI: 10.1159/000540686

INTRODUCTION: FOXO1 plays an important role in regulating immune processes that contribute to allergic inflammation; however, genetic variants influencing FOXO1 expression in AR pathogenesis remains unclear. This study aimed to investigate the functional effect of FOXO1 single nucleotide polymorphisms (SNPs) on AR development 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). We assessed the associations of FOXO1 transcript expression levels in peripheral blood mononuclear cells (PBMC) with AR phenotype, total nasal symptom score (TNSS), and SNP genotype in a sub-cohort of n = 658 individuals from the SMCSGES population. Associations of FOXO1 SNPs with AR were assessed in a cohort of n = 5,072 individuals from the SMCSGES population. In vitro promoter luciferase assay was used to evaluate the effect of AR-associated SNPs on FOXO1 promoter activity.
RESULTS: FOXO1 transcript expression in PBMC was significantly associated with the risk of AR (p < 0.05) and TNSS among AR patients (p < 0.0001). We identified a significant association between tag-SNPs rs9549246 and FOXO1 transcript expression in PBMC from the SMCSGES sub-cohort and the multiethnic eQTLGen consortium (false discovery rate-adjusted p < 0.05). The minor allele "A" of tag-SNP rs9549246 was significantly associated with a higher risk of AR (p = 0.04422, odds ratio = 1.21, 95% confidence interval = 1.01-1.45) in the SMCSGES genotyping cohort (n = 5,072). In vitro luciferase assay showed the minor allele "A" of rs35594717 (tagged by rs9549246) was significantly associated with a higher FOXO1 promoter activity (p < 0.05).
CONCLUSION: FOXO1 transcript expression in PBMC has a strong association with the risk and symptom severity of AR. Genetic variants tagged by rs9549246 were shown to affect the expression of FOXO1 and contribute to the development of AR in the SMCSGES population.
Frequent intake of high fiber and probiotic diets lowers risks associated with atopic dermatitis and house dust mite allergy: a cross-sequential study of young Chinese adults from Singapore and Malaysia

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

Eur J Nutr, 2024 Nov 30;64(1):38.
PMID: 39614888 DOI: 10.1007/s00394-024-03524-6

PURPOSE: Dietary fiber intake may influence the risk and severity of atopic dermatitis (AD), a common chronic allergic skin condition. This cross-sequential study investigated the association between dietary fiber intake and various characteristics of AD, including house dust mites (HDM) allergy and dry skin, in 13,561 young Chinese adults (mean years = 22.51, SD ± 5.90) from Singapore and Malaysia.
METHODS: Dietary habits were assessed using a validated semi-quantitative, investigator-administered food frequency questionnaire from the International Study of Asthma and Allergies in Childhood. We derived an amount-based dietary index to estimate fiber intake while studying its correlation with probiotic drinks intake. AD status was determined by skin prick tests for HDM and symptomatic histories of eczema. Multivariable logistic regression analysis, adjusting for demographic, genetic predisposition, body mass index and lifestyle factors, and synergy factor analysis were used to explore the association and interaction of dietary factors on disease outcomes.
RESULTS: High fiber intake (approximately 98.25 g/serving/week) significantly lowered the associated risks for HDM allergy (Adjusted Odds Ratio [AOR]: 0.895; 95% Confidence Intervals [CI]: 0.810-0.989; adjusted p-value
Fulltext TXK Functional Variants Contribute to Asthma by Regulating Th1 and Th17 Cytokine Pathways

Sio YY, Liu Y, Lam TYW, Say YH, Reginald K, Chew FT

Int Arch Allergy Immunol, 2025 Feb 19.
PMID: 39970891 DOI: 10.1159/000544798

Introduction TXK is involved in the regulation of IFN-γ expression and T helper (Th)1 cell-mediated inflammation that underlies the development of neutrophilic asthma, however, its implication in asthma pathogenesis remains uncertain. This study aims to characterize the functional role of TXK single nucleotide polymorphism (SNP) contributing to asthma. Methods This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Associations of TXK transcript expression with asthma phenotype, the transcript expression of IFN-γ and IL23A, and SNP genotype were assessed in peripheral blood mononuclear cell (PBMC) samples from n=658 individuals of the SMCSGES sub-cohort. Genetic associations of TXK SNPs with asthma were assessed in a case-control cohort of n=2407 individuals from the SMCSGES population. Functional effects of asthma-associated SNPs on TXK promoter activity were evaluated by in vitro promoter luciferase assay in THP-1 cells. Results We identified significant associations of upregulated TXK transcript expression with increased asthma risk (p<0.05) and the increased transcript expressions of both IFN-γ (p<0.0001) and IL23A (p<0.0001) in PBMC. A significant association between tag-SNP rs2661532 and TXK transcript expression was detected in PBMC: the allele "T" was significantly associated with a higher TXK expression than allele "C" (false discovery rate-adjusted p<0.05). The major allele "T" of rs2661532 is also significantly associated with a higher risk of asthma (p=0.0346, odds ratio=1.171, 95% confidence interval=1.011-1.357). The in vitro promoter luciferase assay showed the major alleles of rs6819804 and rs74513879 (tagged by rs2661532) are significantly associated with higher TXK promoter activity (p<0.05). Conclusion This study identified multiple TXK functional variants associated with asthma by regulating the transcript expression of TXK and downstream Th1 and Th17 cell-mediated inflammatory pathways. Our findings indicated the potential involvement of TXK functional variants in the development of neutrophilic asthma.
Associations Between Self-Reported Dietary Intake and Atopic Dermatitis Risk in Young Adults From Singapore and Malaysia

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

Clin Exp Allergy, 2025 Jan 21.
PMID: 39838549 DOI: 10.1111/cea.14629

This cross-sequential study found that frequent intake of high-fat and high-protein foods was associated with higher odds of atopic dermatitis (AD). However, occasional intake across all three macronutrients significantly lowered AD odds, suggesting that moderation-not strict avoidance-may benefit AD management in allergic populations.
Exploratory Analyses of Frequent High-Fat Food Intake in Diets and Its Association with Increased Odds of Atopic Dermatitis in Singapore and Malaysia Young Chinese Adults

Lim JJ, Reginald K, Say YH, Liu MH, Chew FT

Br J Nutr, 2025 Apr 04.
PMID: 40181614 DOI: 10.1017/S0007114525000716

High-fat food intake is associated with atopic dermatitis (AD), but the role of habitual dietary habits related to the frequency of high-fat food intake remains unclear. To address this, we developed a frequency-based dietary index, Diet Quality based on Dietary Fat Score, to assess high-fat food intake and examined its association with AD in 13,561 young Chinese adults (mean age = 22.51 years, SD ± 5.90) from Singapore and Malaysia. Using an investigator-administered questionnaire aligned with the validated International Study of Asthma and Allergy in Childhood protocol, we conducted multivariable logistic regression adjusting for demographics, body mass index, genetic predisposition, and lifestyle factors, with false discovery rate correction for multiple comparisons. Frequent high-fat food intake was associated with higher odds of AD presentation (Adjusted Odds Ratios [AOR]: 1.525; 95% Confidence Intervals [CI]: 1.314-1.772; adjusted p < 0.001). The association remained significant regardless of total fat intake (AOR: 1.445; 95% CI: 1.054-1.801; adjusted p < 0.001) and among individuals with high fruit and vegetable intake (Adjusted Odds Ratios [AOR]: 1.489; 95% Confidence Intervals [CI]: 1.191-1.860; adjusted p < 0.001) or low energy intake (AOR: 1.399; 95% CI: 1.054-1.857; adjusted p < 0.05). No synergistic effects were observed between dietary factors. These findings highlight that frequent intake of high-fat foods is independently associated with AD, emphasizing the importance of dietary moderation in AD risk management.
Whiteleg shrimp-derived Cryptides induce mitochondrial-mediated cytotoxicity in human breast Cancer

El-Aal AAAA, Jayakumar FA, Tan KO, Lahiri C, Chung FF, Reginald K

Bioorg Chem, 2025 Apr 02;160:108432.
PMID: 40199008 DOI: 10.1016/j.bioorg.2025.108432

Breast cancer remains the most prevalent cancer in females. The triple negative subtype of breast cancer is associated with higher recurrence rates and poorer prognosis, lack of effective targeted therapy options, and frequently becoming unresponsive to chemotherapy. This study investigates the in vitro anti-cancer potential of our previously in silico-discovered cryptides, from Penaeus vannamei, against MCF-7, MCF-7-CR, and MDA-MB-231 cancer cell lines. Five cryptides-AD4, AD7, AD8, AD11, and AD12-were tested using the MTT assay, revealing selective toxicity against cancer cells. The lowest and highest calculated IC50 values were for AD12 against MCF-7-CR (∼4.6 μM) and MDA-MB-231 (∼20 μM), respectively. Mechanistic studies showed that the cytotoxicity mediated by cryptides, AD7 and AD8, induced loss of mitochondrial membrane potential, release of mitochondrial cytochrome C, and cleavage of caspases that were associated with BAX activation in MCF-7 and MDA-MB-231 cells. Furthermore, our results showed that both MCF-7 and MDA-MB-231 cells treated with AD7 or AD8 exhibited nuclei condensation, activation of Caspase 3/7, leading to apoptotic cell death associated with intrinsic apoptotic cell signaling mechanism. However, further investigation showed that both AD7 and AD8 peptides promoted up-regulation of FAS and p53 in MCF-7 cells while down-regulated the expression of both FAS and p53 in MDA-MB-231 cells, suggesting cell-type dependent apoptotic cell signaling mechanisms. Moreover, both AD7 and AD8 demonstrated cytotoxic and disintegration effects in 3D cancer model. This study highlights the anticancer potential of marine-derived cryptides against challenging breast cancer subtypes, including triple-negative breast cancer (TNBC), with selective cytotoxicity and potential to overcome resistance and recurrence.

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