Genetically modified foods and allergy

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Peanut oil and peanut allergy, foes or folks?

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Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

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Immunoglobulin G testing in the diagnosis of food allergy and intolerance

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Molecular Diagnosis for Paediatric Genetic Disorders Using Whole Exome Sequencing of the Next Generation Sequencing Technology

Oral PresentationMolecular diagnosis for paediatric genetic diseases is important for targeted or tailored treatment, more informative genetic counselling and guiding the families for prenatal or pre-implantation diagnosis. Traditionally, linkage analysis using large multiplex families or multiple families with the same molecular cause is essential and the process could take years before a diagnosis can be reached. Candidate gene screening is usually the only method available for clinical laboratories for genetic diseases in Hong Kong. Next generation sequencing technology has virtually revolutionised the way genetic studies are conducted and provides opportunities for molecular diagnosis for genetic disorders that were never available before. With the possibility of sequencing the whole genome or almost all the coding exons of the genome, the method does not require the availability of large, multiple affected families and prior knowledge of candidate causal genes. It can be applied to a single patient or, as a usual practice, whole genome or whole exome sequencing for the patient plus parents. For whole exome sequencing (WES), it usually produces up to 100 million short sequencing reads of usually 100bp long. These short reads were firstly compared with sequences of a reference human genome and mapped to genomic regions from which they were generated. Each position (base pair) of a coding exon is usually covered with dozens to hundreds of sequencing reads. Analysing the sequences of these reads allows for identification of mutations that are different from the reference sequences. For WES for a single individual, up to 100,000 variants can be identified, with some of which are common variants in a population and some of which rare or private. The population frequencies of these variants are looked up in public databases such as those from the 1000 Genome Project or ESP6500, a project that sequenced 6500 individuals in the US. An internal database is also established with WES data from 200 samples from the local population. For rare, severe genetic disorders that are likely to be caused by mutations from a single gene, we can safely rule out the common (>1% in a population) variants and only focus on the rare or private variants. The nature of the mutations, such as with or without amino acid changes, changes in the open reading frame of the protein, the nature of the amino acid changes (similarity of the amino acid changed to), the conservation of this amino acid in different species, and the function of the gene in relationship to the disease phenotype, are considered to help pinpoint the causal mutations. We will present examples on using WES for molecular diagnosis for paediatric genetic disorders in our Department. These include detection of de novo mutations (mutations that are not detected in parents), somatic mutations and compound heterozygous mutations, and mutations missed by traditional laboratory testing, which demonstrated the power of this new technology in providing accurate molecular diagnosis.published_or_final_versio

Chinese herbal medicine for functional dyspepsia: systematic review of systematic reviews

© The Author(s), 2018. Background: Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM. Method: We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs. Results: A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported. Conclusion: CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future

Autosomal Dominant Gain-of-function STAT1 Mutation is a Novel Genetic Etiology of Penicillium Marneffei Infection

Symposium / Free Paper 4: ImmunologyConference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesBackground: Penicillium marneffei infection is indigenous to Southeast Asia. Majority of cases occur in patients with AIDS and secondary immunodeficiencies. We previously reported 4 HIV-negative children with chronic mucocutaneous candidiasis (CMC) and severe penicilliosis. Hyper-IgE syndrome was diagnosed in one of them, but extensive genetic studies on IL12-IFNγ axis, CARD9 and AIRE were unrevealing for the rest. Recently, STAT1 hyperphosphorylation causing defective Th1 and Th17 immunity is recognized as a cause of CMC. Objective: To investigate the genetic and functional defects of STAT1 signaling in children affected by penicilliosis. Methods: Targeted sequencing of STAT1 gene or total exome sequencing was performed in 3 patients with CMC and penicilliosis. PBMCs were isolated from patients and normal controls. Intracellular STAT1 phosphorylation (pSTAT1) towards interferon-α and interferon-γ stimulation was evaluated by flow cytometry. Cytokine production in PBMCs towards PMA and ionomycin stimulation was assessed. PBMCs were co-cultured with live Candida albicans and P. marneffei to evaluate interferon-γ response. Results: Heterozygous STAT1 missense mutations were identified in all 3 patients. Two mutations were located in the coiled-coil domain (P1 and P2) and one in the DNA-binding domain (P3). All 3 patients recovered from penicilliosis, but P1 eventually died of fulminant aspergillosis. The percentage of pSTAT1-positive PBMCs induced by interferon-α and interferon-γ was significantly higher in all 3 patients than normal controls, indicating that they had gain-of-function mutations. PBMCs from all patients displayed defective interferon-γ and interleukin-17 production towards PMA and PMA plus ionomycin, respectively. Interferon-γ production induced by C. albicans and P. marneffei in P2 was significantly lower than normal controls. Conclusions: For the first time, we demonstrated STAT1 gain-of-function mutation as an important and novel genetic etiology of invasive mycosis including penicilliosis and aspergillosis. Penicilliosis should be regarded as an indicator disease for primary immunodeficiencies in children without HIV infection unless proven otherwise.published_or_final_versio

Unique pattern of infections in chronic granulomatous disease – The Asian experience

Conference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesSymposium 40: InfectionBackground: Chronic granulomatous disease (CGD) is a phagocytic disorder caused by defective NADPH oxidase activity. Affected individuals are susceptible to bacterial infections, mycosis and hyperinflammatory complications. Variations in the epidemiology of infectious diseases across geographical regions can lead to distinct clinical phenotypes. Objective: To identify the unique clinical characteristics of a large cohort of CGD patients in China and Southeast Asia referred for genetic studies from 2003 to 2012. Methods: 53 patients with genetically-confirmed CGD were included and their clinical features were analyzed. CYBB and CYBA mutations were studied by Sanger sequencing, and NCF1 ‘GT’ deletion hotspot mutation was studied on genomic DNA by GeneScan. Results: 44 patients with X-CGD had CYBB mutations (missense[n=16]; nonsense[n=8]; deletion[n=9]; insertion[n=2]; intron mutation[n=9]). Nine patient had AR-CGD (CYBA[n=5]; NCF1 75_76delGT[n=4]). The median age at presentation and diagnosis was higher in AR-CGD (7m and 66m) compared with X-CGD (3m and 22m). The commonest presentations were pneumonia (58%), skin and perianal abscess (49%), lymphadenitis (42%) and recurrent diarrhea (30%). Aspergillosis and salmonellosis occurred at a frequency similar to published studies (13% and 19% respectively), but the commonest infection was BCG (43%) and 11% had disseminated BCG. 21% of patients had tuberculosis. Fulminant melioidosis and Chromobacterium violaceum infections occurred in 3 patients and two of their male siblings. Hyperinflammatory conditions included polyarthritis (n=3) and pulmonary granuloma (n=2). Death was recorded in 8 patients (15%). Conclusion: Melioidosis and C. violaceum indigenous to Southeast Asia can cause life-threatening infections in CGD patients. The high incidence of mycobacterial infections is associated with universal BCG vaccination and endemicity of tuberculosis. Such observations emphasize the role of respiratory burst as an immune defense mechanism against these pathogens. These infections are seldom reported in Caucasian cohorts, illustrating the importance of regional collaborative studies to facilitate pattern recognition and early diagnosis of primary immunodeficiencies.published_or_final_versio

Impact of COVID-19 pandemic on serum vitamin D level among infants and toddlers: An interrupted time series analysis and before-and-after comparison

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2–24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants’ serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of −6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2–6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period

Kawasaki disease in Hong Kong, 1994 to 2000

OBJECTIVE. To describe the epidemiology, clinical characteristics, and management of Kawasaki disease in children in Hong Kong. DESIGN. Retrospective survey of medical records from July 1994 to June 1997, and prospective data collection from July 1997 to June 2000. SETTING. Hospitals with a paediatric unit in Hong Kong. PATIENTS. Patients diagnosed with Kawasaki disease between July 1994 and June 2000 in public hospitals in Hong Kong. MAIN OUTCOME MEASURES. Incidence of Kawasaki disease and coronary artery aneurysm rates. RESULTS. A total of 696 cases of Kawasaki disease were reported. There were 435 (62.5%) boys and 261 (37.5%) girls giving a male to female ratio of 1.7:1. The age ranged from 1 month to 15 years 5 months with a median of 1.7 years. Infants (<1 year) constituted the largest group of patients (223,32.0%) and overall, 638 (91.7%) were younger than 5 years. Skin rash, conjunctivitis, and oral signs were among the principal clinical features present in over 80% of cases. Prominent cervical lymph nodes larger than 1.5 cm were less commonly found (24%). Coronary artery aneurysms or ectasia were present in 15.7% (109/696), 8.5% (59/696), and 5.0% (35/696) of patients at 2, 4, and 8 weeks, respectively. The incidence of Kawasaki disease per 100 000 children under 5 years was significantly higher in the prospective study period than in the retrospective period (39 vs 26, <0.001). CONCLUSION. The incidence of Kawasaki disease is high in Hong Kong and is 39 per 100 000 children below 5 years of age. The coronary artery aneurysm prevalence is 5%. Intravenous gamma-globulin and high-dose aspirin is the mainstay of treatment.published_or_final_versio