This study reveals the critical role of IgE and IgG4 antibody avidity in distinguishing acute from chronic Anisakis allergy, providing new serological markers for the diagnosis and staging of parasite-related allergic diseases.
Literature Overview
The article 'Antibody Avidity Profiles for Differentiating Acute and Chronic Anisakis simplex—Related Allergic Diseases,' published in the journal Antibodies, reviews and summarizes the use of affinity indices of specific IgE, IgG4, IgG, and IgA antibodies to differentiate clinical phenotypes between acute gastrointestinal allergic anisakiasis (GAA) and chronic urticaria with Anisakis sensitization (CU+). The study evaluates antibody avidity using ELISA and Western blot combined with urea dissociation methods, analyzing their dynamic changes at different disease stages, thus providing crucial evidence for precise diagnosis and immunological mechanism analysis of Anisakis-related allergic diseases.Background Knowledge
Anisakis simplex is a parasitic nematode transmitted through the consumption of raw or undercooked fish, capable of triggering acute gastrointestinal allergic reactions (GAA) or chronic urticaria with sensitization (CU+). Although both conditions involve IgE-mediated allergies, they exhibit significant differences in clinical course and immune response characteristics. Acute GAA typically manifests rapidly after ingestion of infected larvae, presenting abdominal pain, urticaria, or even anaphylactic shock, accompanied by strong polyclonal immune activation; in contrast, CU+ is characterized by long-term, recurrent skin symptoms without a clear history of acute exposure, with a more persistent but weaker immune response. Currently, differentiating between the two remains clinically challenging, especially due to significant cross-reactivity. Antibody avidity (i.e., antigen-antibody binding strength), as a marker of immune maturation, has been used in staging diagnosis for other parasitic diseases (e.g., toxoplasmosis, toxocariasis). However, in Anisakis infection, the dynamics of IgE, IgG4, and other antibody avidities and their indicative value for disease phenotypes have not been systematically assessed. This study fills this gap by being the first to systematically analyze the avidity characteristics of multiple antibody isotypes at different clinical stages, offering a new perspective for optimizing serological diagnostic strategies.
Research Methods and Experiments
The study enrolled 65 patients from the Madrid region, Spain, divided into three groups: acute gastrointestinal allergic anisakiasis (GAA, n=22), chronic urticaria with Anisakis sensitization (CU+, n=22), and non-sensitized chronic urticaria controls (CU−, n=21). Serum samples were collected, and ELISA was used to detect specific IgE, IgG4, IgG, and IgA antibody levels against A. simplex total larval antigens and excretory-secretory (ES) antigens. Avidity indices (AI) of each antibody were determined via urea dissociation ELISA, with AI > 50% defined as high avidity. Additionally, Western blotting was employed to validate antigen recognition profiles and avidity features. Longitudinal follow-up (baseline, 3 months, 1 year) was conducted for GAA and CU+ patients to analyze the dynamic evolution of antibody avidity. Statistical analyses included ANOVA, Mann-Whitney U tests, and correlation analyses to assess associations between avidity and clinical phenotypes or demographic variables.Key Conclusions and Perspectives
Research Significance and Prospects
This study is the first to systematically reveal the dynamic patterns of antibody avidity in Anisakis-related allergic diseases, demonstrating that IgE and IgG4 avidity can serve as reliable serological markers for differentiating acute and chronic phenotypes. Low IgE and high IgG4 avidity suggest acute infection, whereas high and stable IgE avidity with stable IgG4 is more consistent with a chronic sensitization state. These findings not only enhance understanding of the immunopathological mechanisms of A. simplex but also provide practical tools for clinical diagnosis, disease staging, and personalized management.
Future studies could expand sample sizes and include multicenter cohorts to validate the generalizability of these markers across different populations. Combining antigen-specific analyses to identify key antigens driving high-avidity responses may lead to the development of more precise diagnostic reagents. Furthermore, exploring the relationship between IgG4 avidity and immune tolerance could offer new insights into allergy intervention strategies. This approach could also be extended to other parasitic or food allergy models, broadening its applicability.
Conclusion
This study systematically evaluated the avidity characteristics of IgE, IgG4, IgG, and IgA antibodies in patients infected with Anisakis simplex, revealing significant differences in IgE and IgG4 avidity between acute and chronic allergic phenotypes. GAA patients exhibited low IgE avidity and high IgG4 avidity, indicating an immature IgE response and strong helper immune activation during the acute phase; in contrast, CU+ patients displayed high and stable IgE avidity, reflecting the process of antibody maturation under long-term sensitization. Longitudinal data further confirmed that IgE avidity increases over time in the course of GAA, consistent with affinity maturation patterns. Although IgA antibodies were widely present, their avidity failed to effectively differentiate phenotypes. Overall, antibody avidity, especially the measurement of IgE and IgG4, not only enhances the specificity of serological testing but also provides functional indicators for staging and mechanistic studies of Anisakis-related allergic diseases. This method has the potential to become an important complement to clinical differential diagnosis, improving dynamic monitoring of allergic progression and advancing personalized treatment strategies. Future validation in larger cohorts is needed, along with exploration of its potential application in immune-modulating therapies.
