Shrimp Extract Exacerbates Allergic Immune Responses in Mice: Implications on Clinical Diagnosis of Shellfish Allergy.

Tropomyosin has been identified as the major cross-reactive shellfish allergen, but recent studies showed the presence of other clinically relevant allergens. This study aims at determining the allergic immune responses of mice sensitized with raw and boiled shrimp extracts in comparison to recombinant tropomyosin (rTM). Female Balb/c mice were intragastrically sensitized and challenged with raw, boiled shrimp or rTM. Systemic, cellular and humoral allergic responses were compared, while allergenicity of the extracts was also compared by skin prick test (SPT) and immunoblot on shrimp allergic subjects. We showed that rTM and shrimp extracts induced IgE- and Th2-mediated allergic responses in mice, distinguished by remarkable intestinal inflammation in small intestine across all regimens. Notably, boiled shrimp extract exhibited the highest sensitization rate (73.7% of mice developed positive TM-specific IgE response) when compared with raw extract (47.8%) and rTM (34.8%). Mice sensitized with boiled extract manifested the highest allergen-specific IgE and Th2 cytokine responses than the others. Immunoblot results indicated that tropomyosin remained the major allergen in extract-based sensitization and had stronger allergenicity in a heat-treated form comparing to untreated TM, which was in line with the SPT results that boiled extract induced larger wheal size in patients. Hemocyanin and glycogen phosphorylase were also identified as minor allergens associated with manifestation of shrimp allergy. This study shows that boiled extract enhanced sensitization and Th2 responses in agreement with the higher allergenicity of heat-treated TM. This study thus presents three shrimp allergy murine models suitable for mechanistic and intervention studies, and in vivo evidence implies higher effectiveness of boiled extract for the clinical diagnosis of shellfish allergy.

Variation in Shrimp Allergens: Place of Origin Effects on Food Safety Assessment.

Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected by an origin-dependent protein composition. This study determined if the geographic location of capture, or aquaculture, influenced the allergenic protein profiles of Black Tiger Shrimp (Penaeus monodon), one of the most farmed and consumed shrimp species worldwide. Protein composition was analysed in shrimp from nine different locations in the Asia-Pacific by SDS-PAGE, immunoblotting, and mass spectrometry. Ten of the twelve known shrimp allergens were detected, but with considerable differences between locations. Sarcoplasmic calcium-binding protein, myosin light chain, and tropomyosin were the most abundant allergens in all locations. Hemocyanin-specific antibodies could identify up to six different isoforms, depending on the location of origin. Similarly, tropomyosin abundance varied by up to 13 times between locations. These findings suggest that allergen abundance may be related to shrimp origin and, thus, shrimp origin might directly impact the readout of commercial crustacean allergen detection kits, most of which target tropomyosin, and this should be considered in food safety assessments.

IgE-Mediated Shellfish Allergy in Children.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed.

A comprehensive overview of emerging processing techniques and detection methods for seafood allergens.

Seafood is rich in nutrients and plays a significant role in human health. However, seafood allergy is a worldwide health issue by inducing adverse reactions ranging from mild to life-threatening in seafood-allergic individuals. Seafood consists of fish and shellfish, with the major allergens such as parvalbumin and tropomyosin, respectively. In the food industry, effective processing techniques are applied to seafood allergens to lower the allergenicity of seafood products. Also, sensitive and rapid allergen-detection methods are developed to identify and assess allergenic ingredients at varying times. This review paper provides an overview of recent advances in processing techniques (thermal, nonthermal, combined [hybrid] treatments) and main allergen-detection methods for seafood products. The article starts with the seafood consumption and classification, proceeding with the prevalence and symptoms of seafood allergy, followed by a description of biochemical characteristics of the major seafood allergens. As the topic is multidisciplinary in scope, it is intended to provide information for further research essential for food security and safety.

Survey of Tetrodotoxin in New Zealand Bivalve Molluscan Shellfish over a 16-Month Period.

Tetrodotoxin (TTX) is a heat-stable neurotoxin typically associated with pufferfish intoxications. It has also been detected in shellfish from Japan, the United Kingdom, Greece, China, Italy, the Netherlands and New Zealand. A recent European Food Safety Authority (EFSA) scientific opinion concluded that a level of <0.044 mg TTX/kg in marine bivalves and gastropods, based on a 400 g portion size, does not result in adverse effects in humans. There have been no reports of human illness attributed to the consumption of New Zealand shellfish containing TTX. To obtain a greater understanding of its presence, a survey of non-commercial New Zealand shellfish was performed between December 2016 and March 2018. During this period, 766 samples were analysed from 8 different species. TTX levels were found to be low and similar to those observed in shellfish from other countries, except for pipi (Paphies australis), a clam species endemic to New Zealand. All pipi analysed as part of the survey were found to contain detectable levels of TTX, and pipi from a sampling site in Hokianga Harbour contained consistently elevated levels. In contrast, no TTX was observed in cockles from this same sampling site. No recreationally harvested shellfish species, including mussels, oysters, clams and tuatua, contained TTX levels above the recommended EFSA safe guidance level. The levels observed in shellfish were considerably lower than those reported in other marine organisms known to contain TTX and cause human intoxication (e.g., pufferfish). Despite significant effort, the source of TTX in shellfish, and indeed all animals, remains unresolved making it a difficult issue to understand and manage.

Shellfish Allergy: Unmet Needs in Diagnosis and Treatment.

Seafood is a major cause of food allergy and anaphylaxis worldwide. Shellfish is included among the "big eight" food groups, which are responsible for more than 90% of all cases of food allergy. Approximately 2.5% of the world's population has experienced an adverse reaction to seafood. Seafood allergy is one of the most frequent and lethal allergies that exist. The several allergenic proteins involved in allergic reactions that have been described in recent years include tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein. Despite all the data reported in the last few years, shellfish allergy is still diagnosed and treated as it was 50 years ago. The only effective treatment to prevent allergic reactions to shellfish is avoidance. This review aims to update recently published data on shellfish allergy and to highlight those areas that have yet to be resolved.

Identification and Cross-reactivity Analysis of Sarcoplasmic-Calcium-Binding Protein: A Novel Allergen in Crassostrea angulata.

Oysters are an important shellfish group known to cause food allergy; however, knowledge of their sensitization components and cross-reactivity is limited. This study aimed to identify a novel allergen in Crassostrea angulata and investigate its cross-reactivity. To this end, a 20 kDa protein was purified from oyster and confirmed to be a sarcoplasmic-calcium-binding protein (SCP) by LC-MS/MS. A 537 bp open reading frame was obtained from oyster SCP total RNA, which encoded 179 amino acids, and was expressed in Escherichia coli. According to the circular dichroism results, digestion assay, and inhibition ELISA, the recombinant SCP (rSCP) exhibited similar physicochemical properties and IgG-binding activity to native SCP. rSCP displayed stronger IgE-binding activity by immunological method. Moreover, a different intensity of cross-reactivity and sequence homology were demonstrated between shellfish species. Collectively, these findings provide novel insight into shellfish allergens, which can be used to aid in the in vitro diagnosis of oyster-sensitized patients.

Overcoming Shellfish Allergy: How Far Have We Come?

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a "cure "for shellfish allergy is within reach.

Dietary mercury intake and colorectal cancer risk: A case-control study.

BACKGROUND & AIMS: The main source of mercury exposure is food such as fish and shellfish. Mercury is a growing concern due to its associations with a number of harmful health effects, including cancer. The objectives of this study were to examine the association between dietary mercury intake and colorectal cancer (CRC) risk and to determine whether this association differs by anatomical site and menopausal status. METHODS: A case-control study was conducted with 2769 participants (923 cases and 1846 controls) in Korea. Dietary mercury intake and fish and shellfish consumption were assessed using a semiquantitative food frequency questionnaire. RESULTS: A high intake of dietary mercury was associated with an increased risk of CRC (in the group with lower fish and shellfish consumption; odds ratio (OR): 3.13; 95% confidence interval (95% CI): 2.33, 4.71, in the group with higher fish and shellfish intake; OR: 3.84, 95% CI: 2.20, 7.30) after adjusting for all potential confounders by anatomic site in men. Among women, the results differed by fish and shellfish consumption and menopausal status. Regarding the amount of fish and shellfish intake, a positive association was found only in the group with lower intake (CRC; OR: 2.24, 95% CI: 1.36, 3.72, colon cancer; OR: 2.25, 95% CI: 1.22, 4.16, rectal cancer; OR: 2.28, 95% CI: 1.13, 4.57). In the stratified analysis by menopausal status, the elevated risk of CRC was still observed among both pre- and postmenopausal women depending on anatomical site, except for the colon cancer patients with premenopausal status. CONCLUSIONS: A high intake of mercury was associated with an elevated risk of overall CRC. Future large-scale prospective cohort studies are recommended to investigate the causal effects of dietary mercury intake by fish and shellfish consumption on CRC risk depending on anatomical site and menopausal status.

BET 2: Is there an association between iodine, shellfish and contrast agent allergies?

A shortcut review was carried out to establish whether having a shellfish or iodine allergy changed the risk of allergic reaction in patients receiving radiocontrast medium more than other concomitant allergies. One relevant paper (a systematic review) was identified for inclusion using the reported search strategy. The author, date and country of publication; group studied; study type; relevant outcomes; results and study weaknesses of this paper are tabulated. It is concluded that there is no evidence that allergy to shellfish or iodine alters the risk of reaction to intravenous contrast more than any other allergies.

Association between food allergy and ankylosing spondylitis: An observational study.

Food allergies can alter the gut microbiome composition, increasing the risk of conditions such as ankylosing spondylitis (AS).To identify the association between specific allergens and AS, we investigated the differences in the serum levels of 14 food antigen-specific immunoglobulin (Ig) G between AS patients and healthy participants. The association between the levels of these antibodies and disease activity was assessed by measuring the inflammatory marker C-reactive protein (CRP).We enrolled 75 AS patients and 78 healthy controls who had undergone antigen-specific IgG tests in West China Hospital between January 2015 and October 2017, and performed enzyme-linked immunosorbent assays for specific IgG against 14 food allergens: rice, egg, mushroom, milk, pork, chicken, beef, crab, codfish, corn, soybean, tomato, shrimp, and wheat. The following tests were used to analyze differences between AS patients and healthy controls: χ test for sex, and a 2-tailed Student t-test or Mann-Whitney U test based on the results of Levene test for age and IgG levels. Correlations between IgG and CRP levels were calculated using a Spearman's correlation.AS patients had significantly higher serum levels of beef-, crab-, and pork-specific IgG than did healthy participants. In addition, the serum levels of pork-specific IgG were significantly and positively correlated with CRP.These results suggest that α-Gal, the predominant natural antigen in mammalian red meat, might play a potential role in the pathogenesis of AS, and therefore, AS patients should exclude such allergenic foods, including beef, crab and pork, from their daily diet.

Fish/shellfish intake and the risk of head and neck cancer.

Fish intake and other dietary sources of omega-3 fatty acids have been shown to be associated with a reduced risk for some cancers. Although previous studies of head and neck cancer have reported associations with different dietary factors, including reduced risks for fruits and vegetables and putatively healthy dietary patterns, associations specific to fish intake are unclear. This study investigated the association between fish/shellfish intake and risk of squamous cell carcinoma of the head and neck (SCCHN) using data from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study conducted in 46 North Carolina counties with cases recruited from 2002 through 2006. Controls were frequency matched to the cases on age, sex, and race; the final sample size was 1039 cases and 1375 controls. Demographic, lifestyle, and dietary information were collected using an in-person interviewer-administered structured questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with unconditional logistic regression. Patients whose fish/shellfish intake was among the highest tertile had a 20% lower odds of SCCHN compared with those in the lowest tertile (OR: 0.80; 95% CI: 0.60-1.07) after adjustment for the matching and other factors (income, energy intake, fruit intake, cigarette smoking, and alcohol intake). The inverse association was more pronounced for oral cavity and oropharyngeal tumors, for African Americans, and for females, but CIs were wide. To further investigate this potential risk reduction strategy for SCCHN, future studies should consider examining specific fish/shellfish, cooking practices, and other omega-3 fatty acid sources.

First detection of tetrodotoxin and high levels of paralytic shellfish poisoning toxins in shellfish from Sicily (Italy) by three different analytical methods.

Paralytic shellfish toxins (PST) and tetrodotoxin (TTX) are naturally-occurring toxins that may contaminate the food chain, inducing similar neurological symptoms in humans. They are co-extracted under the same conditions and thus their combined detection is desirable. Whilst PST are regulated and officially monitored in Europe, more data on TTX occurrence in bivalves and gastropods are needed before meaningful regulations can be established. In this study, we used three separate analytical methods - pre-column oxidation with liquid chromatography and fluorescence detection, ultrahigh performance hydrophilic interaction liquid chromatography (HILIC) tandem mass spectrometry (MS/MS) and HILIC high resolution (HR) MS/MS - to investigate the presence of PST and TTX in seawater and shellfish (mussels, clams) collected in spring summer 2015 to 2017 in the Mediterranean Sea. Samples were collected at 10 sites in the Syracuse Bay (Sicily, Italy) in concomitance with a mixed bloom of Alexandrium minutum and A. pacificum. A very high PST contamination in mussels emerged, unprecedentedly found in Italy, with maximum total concentration of 10851 µg saxitoxin equivalents per kg of shellfish tissue measured in 2016. In addition, for the first time TTX was detected in Italy in most of the analysed samples in the range 0.8-6.4 µg TTX eq/kg. The recurring blooms of PST-producing species over the 3-year period, the high PST levels and the first finding of TTX in mussels from the Syracuse bay, suggest that monitoring programmes of PST and TTX in seafood should be activated in this geographical area.

Prenatal and Early Postnatal Exposure to Total Mercury and Methylmercury from Low Maternal Fish Consumption.

The aim of this study was to investigate the influence of low fish consumption on prenatal and early postnatal exposure to mercury species. The samples of umbilical cord blood and maternal milk as well as interviewer-administered questionnaires were collected from 142 Slovak mother-child pairs. The mean total mercury (THg) concentrations in cord blood and milk were 0.949 µg/L and 0.376 µg/kg, respectively. The mean methylmercury (MeHg) concentration in cord blood was 0.504 µg/L. Fish eaters had significantly higher cord blood MeHg concentrations than non-fish eaters (p = 0.030); no difference was found in milk or cord blood THg concentrations. The bivariate analysis showed a positive correlation between cord blood MeHg and consumption of sea fish and shellfish (rs = 0.320, p < 0.001); after adjustment for the potential confounders, the association was weakened (ß = 0.173, p = 0.059). Nevertheless, the decision tree method showed sea fish and shellfish consumption to be the best predictor of cord blood MeHg. Furthermore, a negative association was found between THg concentrations in maternal milk and freshwater fish consumption (ß = - 0.193, p = 0.017), which might indicate a beneficial effect of freshwater fish consumption. The results suggest there is a need for future research to investigate the benefits versus the adverse effects of low maternal fish consumption on child development.

Allergic myocardial infarction: Type I Kounis syndrome following blue crab consumption.

Objectives: Allergic myocardial infarction, known as Kounis syndrome, is an acute myocardial infarction after an allergic reaction to food, drugs, or insect stings, etc. Kounis syndrome can also be caused by all kinds of seafood, such as finned fish, molluscan shellfish, cephalopods, and crustacean shellfish. Methods: Herein, we report a case of a 67-year-old man, with hypertension, referred for itchiness, facial rash, chest pain, and palpitations developed after consumption of blue crab. Results: Electrocardiogram showed ST elevations in leads II,III,aVF. Transthoracic echocardiography revealed inferior wall hypokinezia with a left ventricular ejection fraction of 55%. Coronary angiography revealed no sign of atherosclerosis. The patient was diagnosed to have Kounis Syndrome type I variant, secondary to blue crab ingestion. He was treated with oral antihistamines and prednisolone.The repeated cardiac markers were within normal limits, with resolution of electrocardiographic abnormalities and inferior wall motion echocardiographic changes. Conclusion: All patients admitted to the emergency department with chest pain and ST elevation on electrocardiography should be asked about allergic insults.

Maillard reaction with ribose, galacto-oligosaccharide or chitosan-oligosaccharide reduced the allergenicity of shrimp tropomyosin by inducing conformational changes.

Tropomyosin (TM), the predominant shellfish allergen, has induced severe food allergy worldwide, but efficient prevention and cure measures are limited nowadays. In the present study, we introduced an approach to eliminate Penaeus chinensis TM by Maillard reaction with reducing sugars including ribose, galacto-oligosaccharide (GOS) and chitosan-oligosaccharide (COS), which reduced the allergenicity by up to 60%. We also evaluated the conformational changes of TM during reaction by far-UV circular dichroism, and found the reaction-induced alternation from α-helix to ß-sheet. We further determined the effect of Maillard reaction on TM allergenic epitopes to investigate the detailed mechanisms, and revealed the structure preference of different sugars. Correlation analysis with experimental data revealed that α-helix mediated the allergenicity elimination by Maillard reaction. There results provided theoretical foundations for the improvement and application of Maillard reaction in allergenic food processing.

Gender-specific risk factors for gout: a systematic review of cohort studies

Abstract Background: Though gout is more prevalent in men than women, it remains unclear whether gender influences risk factors for incident gout. We aimed to systematically review all cohort studies examining risk factors for the development of gout by gender. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched from inception to March 2019. Risk factors for gout examined were: age, ethnicity, consumption of alcohol, meat, seafood, dairy products, purine-rich vegetables, coffee and fructose, vitamin C intake, the Dietary Approaches to Stop Hypertension (DASH) diet, metabolic syndrome, BMI, waist and chest circumference, waist-to-hip ratio, weight change, diabetes mellitus, dyslipidaemias, renal disease, psoriasis, hypertension, diuretic use and anti-diabetic medication. Cohort studies were included if examining (at least) one of these risk factors for gout in either gender in the general population or primary care. Sample characteristics from included articles and their reported risk estimates were described using narrative synthesis. Results: Thirty-three articles were included, 20 (60.6%)directly compared risk factors by gender, 10 (30.3%) used men-only samples, 3 (9.1%) used women-only samples. Articles comparing risk across genders found similar increases in most risk factors. However, in men, metabolic syndrome (Hazard Ratio (95% CI) 1.37(1.20-1.58)) presented a risk of incident gout compared to none in women (> 50 years 1.15(0.85-1.54); ≤50 years 1.29(0.76-2.17)). Compared to men, women showed greater associated risk with higher consumption of fish and shellfish (HR (95% CI) Men: 1.02 (0.86-1.22); Women 1.36 (1.12-1.65)). Conclusions: Risk factors for developing gout did not typically differ between genders and therefore similar preventative advice can be provided. Exceptions were metabolic syndrome in men and excessive seafood consumption in women, but these singular articles need further examination and in general more research into the risk factors for gout which includes women is required.

Exposure assessment to paralytic shellfish toxins through the shellfish consumption in Korea.

Paralytic shellfish poisoning is caused by saxitoxin and its analogues. The paralytic shellfish toxins (PSTs) are produced by marine dinoflagellates and can be accumulated in filter feeding shellfish, such as mussel, clam, oyster and ark shell. The worldwide regulatory limits for PSTs in shellfish are set at 80 µg STX eq./100 g meat and this is widely accepted as providing adequate public health protection. In this study, we have determined five individual PSTs (STX, GTX1, GTX2, GTX3 and GTX4) in shellfish using LC-MS/MS and assessed the human acute and chronic exposures to PSTs through shellfish consumption. Food consumption data was obtained from the Korea National Health and Nutrition Examination Survey (KNHANES 2010-2015). The acute exposure using a large portion size of 88 g/day (95th percentile for consumers only) with maximum toxin level of 198.7 µg/kg was 0.30 µg/kg bw. Even though we estimated the acute exposure with a conservative manner, it was below the ARfDs (0.5 or 0.7 µg STX eq./kg bw) proposed by the international organizations, representing 43-60% of the ARfDs. The chronic exposures using mean consumption data for whole population with mean concentration of PSTs were ranged from 0.002 to 0.026 µg STX eq./kg bw/day. For consumers only, the chronic exposures were in the range of 0.012-0.128 µg STX eq./kg bw/day.