A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population.

BACKGROUND: Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present study aimed to investigate causal correlation of the two diseases by a Mendelian randomization (MR) study and further elucidate the underlying molecular mechanisms. METHODS: With the biggest summary datasets of a genome-wide association study (GWAS) in the East Asian population, we conducted a two-sample, bidirectional MR study to assess the causal correlation between shrimp allergy (SA) and MDD. Subsequently, we identified the pleiotropic genes' susceptibility to the two diseases at whole-genome and tissue-specific levels, respectively. Enriched GO sets and KEGG pathways were also discovered to elucidate the potential underlying mechanisms. RESULTS: With the most suitable MR method, SA was identified as a causal risk factor for MDD based on three different groups of independent genetic instruments, respectively (p < 2.81 × 10-2). In contrast, we did not observe a significant causal effect of MDD on SA. The GWAS-pairwise program successfully identified seven pleiotropic genetic variants (PPA3 > 0.8), indicating that the two diseases indeed have a shared genetic basis. At a whole-genome level, the MAGMA program identified 44 pleiotropic genes, which were enriched in allergy-related pathways, such as antigen processing and presentation pathway (p = 1.46 × 10-2). In brain-specific tissue, the S-MultiXcan program found 17 pleiotropic genes that were significantly enriched in immune-related pathways and GO sets, including asthma-related pathway, T-cell activation-related, and major histocompatibility complex protein-related GO sets. Regarding whole-blood tissue, the program identified six pleiotropic genes that are significantly enriched in tolerance induction-related GO sets. CONCLUSIONS: The present study for the first time indicated a significant causal effect of SA on the occurrence of MDD, but the reverse was not true. Enrichment analyses of pleiotropic genes at whole-genome and tissue-specific levels implied the involvement of allergy and immune-related pathways in the shared genetic mechanism of the two diseases. Elucidating the causal effect and the acting direction may be beneficial in reducing the incidence rate of MDD for the massive group of SA patients in the East Asian region.

Association of HLA-DQ and IL13 gene variants with challenge-proven shrimp allergy in West Bengal, India.

Little is known about genetic factors and mechanisms underlying shrimp allergy. Genome-wide association studies identified HLA class-II and IL13 genes as highly plausible candidates for shrimp allergy. The present study was designed to investigate potential associations of HLA-DQ rs9275596, IL13 rs20541, and IL13 rs1800925 polymorphisms with challenge-proven shrimp allergy using the data from 532 people of West Bengal, India; selected on basis of positive skin prick test, elevated specific IgE and medical history. Risk genotypes, i.e., HLA-DQ rs9275596 CC, IL13 rs20541 AA, and IL13 rs1800925 TT, were found to be significantly associated with challenge positive shrimp allergy (P = 0.04, 0.01, and 0.03, respectively). Distribution of genotypes for HLA-DQ and IL13 polymorphisms in allergic and control subjects showed significant difference between younger (20-40 years) and older (> 40 years) age group (P = 0.006). Risk genotypes significantly associated with elevated shrimp-specific IgE. IL13 TA haplotype significantly associated with shrimp allergy and elevated specific IgE (P = 0.02). Synergistic effect of IL13 TA haplotype-HLA-DQ rs9275596 CC genotype interaction significantly elevated specific IgE (P = 0.03). The present study suggests that HLA-DQ and IL13 polymorphisms pose major risk for shrimp allergic patients in West Bengal, India and thus could be helpful for early target-specific therapeutic intervention in near future.

IgE and IgG4 responses to shrimp allergen tropomyosin and its epitopes in patients from coastal areas of northern China.

Sensitization to allergens and their peptides varies among patients due to geographical or ethnic differences. The present study aimed to investigate immunoglobulin (Ig)E and IgG4 responses to tropomyosin and its peptides in shrimp allergic patients from northern China. A total of 92 subjects were studied, including 35 shrimp allergic patients, 29 patients with house dust mite (HDM) and/or cockroach allergic patients and 28 healthy volunteers. Serum IgE and IgG4 antibodies to recombinant shrimp tropomyosin (rPen a 1) and its peptides were measured by means of a light­initiated chemiluminescent assay. A total of 9 major sequential epitopes of Pen a 1 reported in the literature were synthesized. Of 35 shrimp allergic patients, 25 (71.4%) had positive Pen 1­specific IgE (sIgE) antibodies and 22 (62.9%) contained measurable rPen a 1­specific IgG4 (sIgG4) antibodies. A strong IgG4 response accompanied the presence of IgE to Pen a 1. None of the patients with HDM and/or cockroach allergy demonstrated IgE reactivity to rPen a 1. The reaction frequency of IgE binding epitope was 20­48%, while that of IgG4 binding epitope was 63.6­90.9%. The IgE and IgG4 recognition patterns of the tropomyosin peptides demonstrated high interpatient heterogeneity. Diversity of IgE binding epitopes was positively correlated with Pen a 1 sIgE levels. In the study population, tropomyosin was a major allergen recognized by the majority of shrimp allergic patients, which is consistent with previous reports. However, none of the 9 epitopes are major (reaction frequency >50%) IgE­binding regions, indicating the epitopes profile may be different in other regions.

An update on shellfish allergy.

PURPOSE OF REVIEW: Shellfish is an important cause of food allergy worldwide, and a major cause of food-triggered anaphylaxis. Despite the wide variety of shellfish, there is considerable serological and clinical cross-reactivity of major shellfish allergens, and accurate diagnosis remains a challenge in the management of shellfish allergy. RECENT FINDINGS: Novel minor allergens have been discovered and characterized, and advances in component resolved diagnostics have provided insights into the prevalence of sensitization and their clinical importance in shellfish allergy. The extensive cross-reactivity between tropomyosin of house-dust mite and crustacean shellfish has been postulated to be the cause of a proposed mite-shellfish oral allergy syndrome. SUMMARY: More studies in food challenge-proven patients are required to establish the true prevalence and natural history of shellfish allergy. Refinement of component resolved diagnostics and testing for minor allergens may be helpful in developing more precise species-specific tests. Further investigation into the role of tropomyosin in house-dust mite and shellfish allergies may provide novel immunotherapeutic approaches for shellfish allergy.

Allergen immunotherapy for food allergy from the Asian perspective: key challenges and opportunities.

Introduction: Prevalence of food allergy is rising in different regions of the world. Asia has not been spared from this epidemic, but epidemiological data have revealed a different pattern of food allergens in this continent. Allergen-specific immunotherapy (AIT) for food allergy, which has been revolutionary as the main focus of research in recent years, needs to be adapted for the different populations in Asia. Areas covered: Recent evidence shows increasing popularity and superiority of AIT over strict food avoidance as the cornerstone of food allergy management. Asia is a distinctive continent with specific food allergy triggers, in particular, seafood, and wheat. Peanut, on the contrary, is not a common food allergen in most parts of Asia. The common Asian food allergens, as well as the rapidly developing food-specific AIT in this region will be covered in this article. Expert commentary: Evidence on oral immunotherapy for wheat allergy and preclinical data on shellfish AIT are promising. Further work should be done on resolving cross-sensitization between environmental allergens with wheat and shellfish allergens, and a modified AIT approach to enhance the safety and effectiveness of food-specific immunotherapy.

Seafood-Associated Shellfish Allergy: A Comprehensive Review.

Shellfish are diverse, serve as main constituents of seafood, and are extensively consumed globally because of their nutritional values. Consequently, increase in reports of IgE-mediated seafood allergy is particularly food associated to shellfish. Seafood-associated shellfish consists of crustaceans (decapods, stomatopods, barnacles, and euphausiids) and molluskans (gastropods, bivalves, and cephalopods) and its products can start from mild local symptoms and lead to severe systemic anaphylactic reactions through ingestion, inhalation, or contact like most other food allergens. Globally, the most commonly causative shellfish are shrimps, crabs, lobsters, clams, oysters, and mussels. The prevalence of shellfish allergy is estimated to be 0.5-2.5% of the general population but higher in coastal Asian countries where shellfish constitute a large proportion of the diet. Diversity in allergens such as tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic binding protein are from crustaceans whereas tropomyosin, paramyosin, troponin, actine, amylase, and hemoyanin are reported from molluskans shellfish. Tropomyosin is the major allergen and is responsible for cross-reactivity between shellfish and other invertebrates, within crustaceans, within molluskans, between crustaceans vs. molluskans as well as between shellfish and fish. Allergenicity diagnosis requires clinical history, in vivo skin prick testing, in vitro quantification of IgE, immunoCAP, and confirmation by oral challenge testing unless the reactions borne by it are life-threatening. This comprehensive review provides the update and new findings in the area of shellfish allergy including demographic, diversity of allergens, allergenicity, their cross-reactivity, and innovative molecular genetics approaches in diagnosing and managing this life-threatening as well as life-long disease.

Risk factors in pediatric shrimp allergy.

BACKGROUND: The prevalence of shellfish allergy is ∼1.3% in the United States, with shrimp most commonly reported. Shellfish is one of the top causes of food-induced anaphylactic reactions, yet there are no reported rates of pediatric shrimp anaphylaxis in the literature. In previously reported adults with shrimp allergy, the rate of anaphylaxis to shrimp was 42%. OBJECTIVE: To describe the rate of anaphylaxis among children with shrimp allergy, demographics, clinical presentation, and cross-reactive sensitization. METHODS: Retrospective chart review of children ≤18 years old who presented with shrimp allergy to Texas Children's Hospital Allergy and Immunology Clinic over 11 years. RESULTS: Sixty-eight patients were identified with shrimp allergy (61% male, 39% female), with a median age of diagnosis at 5.6 years (range, 0.96-16.6 years). The rate of anaphylaxis was 12%, and mucocutaneous symptoms were most common (skin symptoms, 70%; urticaria, 58%; and angioedema, 58%). No factors were positively associated with anaphylaxis, whereas patients without anaphylaxis had a significantly higher rate of eczema compared with those with anaphylaxis (p = 0.02). African Americans and Asian Americans were disproportionately affected (p < 0.001). There were low rates of cross-sensitization for other crustaceans and for mollusks (57% and 26%, respectively). CONCLUSION: The rate of anaphylaxis to shrimp was significantly lower in children with shrimp allergy than in adults, and anaphylactic reactions were negatively associated with eczema. Cross-reactivity to other crustaceans and mollusks does not uniformly occur. Prospective studies with double blinded placebo-controlled food challenges are needed to further characterize patients with shrimp allergy.

Fish and shellfish allergy.

Fish and shellfish consumption has increased worldwide, and there are increasing reports of adverse reactions to fish and shellfish, with an approximate prevalence of 0.5-5%. Fish allergy often develops early in life, whilst shellfish allergy tends to develop later, from adolescence onwards. Little is known about the natural history of these allergies, but both are thought to be persistent. The clinical manifestations of shellfish allergy, in particular, may vary from local to life-threatening 'anaphylactic' reactions within an individual and between individuals. Parvalbumin and tropomyosin are the two major allergens, but several other allergens have been cloned and described. These allergens are highly heat and biochemically stable, and this may in part explain the persistence of these allergies. Diagnosis requires a thorough history, skin prick and in-vitro-specific IgE tests, and oral challenges may be needed for diagnostic confirmation. Strict avoidance of these allergens is the current standard of clinical care for allergic patients, and when indicated, an anaphylactic plan with an adrenaline auto-injector is prescribed. There are no published clinical trials evaluating specific oral immunotherapy for fish or shellfish allergy.

Prevalence of Peanut, Tree Nut, Sesame, and Seafood Allergy in Mexican Adults.

OBJECTIVE: To identify the prevalence of perceived and probable allergic reactions to peanuts, tree nuts, sesame seed, or seafood and its association with the personal history of allergic disease. METHODS: A cross-sectional study was performed in four cities of the metropolitan area of Guadalajara, located in western Mexico. Through sampling by gender and age, 1,126 subjects were included. Using a structured questionnaire, we investigated: (i) history of atopic disease, (ii) perception of allergic reaction after food intake, and (iii) probable allergic reaction to peanuts, tree nuts, sesame, or seafood. Prevalence and 95% confidence intervals were calculated. A multivariate analysis of factors associated to perceived and probable allergic reactions to food was performed by logistic regression. RESULTS: Men were 49.8%; mean age was 28.1 years; personal history of atopic disease included: allergic rhinitis (6.9%), asthma (6.8%), and atopic dermatitis (3.8%). Prevalence of perceived and probable food allergy was, respectively: pecan 0.4 and 0.3%; peanut 0.6 and 0.6%; sesame 0.1 and 0.1%; shellfish 4.2 and 4.0% (mainly shrimp); mollusk 0.8 and 0.7%; fish 1.4 and 1.2%. Asthma was significantly associated with perceived and probable allergy to pecans, peanuts, fish, or seafood. Atopic dermatitis was associated with perceived and probable allergic reaction to sea snail, seafood, shellfish, or mollusks. Finally, allergic rhinitis was associated with allergy to shrimp and crustaceans. CONCLUSIONS: This study shows that the prevalence of peanut, tree nut, sesame seed, and seafood allergy in this Mexican population is similar to that reported in developed countries.