This study systematically summarizes the application of various immunochemical methods for detecting specific IgE and IgG autoantibodies in patients with chronic spontaneous urticaria (CSU), providing important guidance for experimental design and clinical subtyping strategies in autoimmune skin diseases.
Literature Overview
The article “Immunochemical Determination of IgE and IgG Autoantibodies in Patients with Chronic Spontaneous Urticaria: A Narrative Review”, published in the journal Antibodies, systematically explores the autoimmune mechanisms mediated by IgE and IgG autoantibodies in chronic spontaneous urticaria (CSU), with a focus on immunochemical techniques used to detect these autoantibodies, particularly the application of ELISA. The article further analyzes the value of these detection methods in CSU endotype classification, disease activity assessment, and treatment response prediction, providing theoretical support for clinical translation.Background Knowledge
Chronic spontaneous urticaria (CSU) is an immune-mediated skin disorder of unknown etiology, characterized by recurrent episodes of wheals or angioedema lasting more than six weeks, significantly impairing patients’ quality of life. Although most cases lack identifiable triggers, increasing evidence indicates that approximately 30%–40% of CSU patients have an autoimmune background, in which abnormal activation of IgE and IgG autoantibodies plays a key role in disease pathogenesis. Current treatment for CSU primarily relies on antihistamines and omalizumab; however, a subset of patients responds poorly, highlighting the disease’s heterogeneity and the urgent need for reliable biomarkers for endotyping. Existing detection methods such as the autologous serum skin test (ASST) and basophil activation test (BAT) suffer from technical complexity and poor reproducibility, while standardized commercial assay kits are not yet widely available, limiting the clinical implementation of autoantibody testing. Therefore, developing stable and reproducible immunochemical detection methods, especially for IgE and IgG autoantibodies targeting key autoantigens such as FcεRI, IgE, TPO, has become a crucial entry point for precise subtyping and personalized therapy.
Research Methods and Experiments
The authors conducted a systematic review of literature published between 2019 and 2025, extracting various immunochemical detection methods, with a focus on ELISA and its variants for detecting specific IgE and IgG autoantibodies in the serum of CSU patients. The study summarizes several “in-house” ELISA methods, such as those detecting IgE autoantibodies against tissue transglutaminase 2 (Tg2), thyroid peroxidase (TPO), eosinophilic proteins (EPX, ECP), and the high-affinity IgE receptor (FcεRI). It also reviews ELISA, chemiluminescence immunoassay (CLIA), and immunoblotting techniques for detecting IgG autoantibodies against antigens such as IgE, FcεRI, and TPO. These methods are not only used to detect specific antibodies but are also combined with total IgE (tIgE) level measurements to construct comprehensive biomarker models. The study further analyzes the value of these methods in predicting response to omalizumab, for example, a high anti-TPO-IgG/low tIgE ratio is associated with non-response.Key Conclusions and Perspectives
Research Significance and Prospects
This study underscores the central role of precise immune endotyping in CSU management. By establishing standardized immunochemical testing protocols, it becomes possible to differentiate between IgE- and IgG-mediated autoimmune mechanisms, facilitating a shift from “symptom control” to “mechanism-directed therapy.” For instance, type I CSU patients may benefit more from anti-IgE therapy, whereas type IIb patients might require interventions targeting the IgG pathway, such as BTK inhibitors or immunosuppressants.
Moreover, the review offers new perspectives for drug development: pathogenic IgG autoantibodies targeting FcεRI or IgE could become targets for novel biologics. Additionally, establishing stable and reliable detection platforms will enable dynamic monitoring of disease activity and treatment response in clinical practice, enhancing personalized management. Future research should focus on multicenter validation of existing methods and their commercialization to enable translation from research to clinical application.
Conclusion
This article systematically reviews the application of immunochemical methods in chronic spontaneous urticaria (CSU), revealing the critical role of specific IgE and IgG autoantibodies in disease endotyping and treatment prediction. By detecting autoantibodies such as anti-TPO-IgE and anti-FcεRI-IgG, and combining them with tIgE levels, it is possible to effectively distinguish between type I, type IIb, and overlap forms of CSU, providing a basis for personalized treatment strategies. Notably, a high anti-TPO-IgG/low tIgE ratio has been shown to predict omalizumab treatment failure, offering significant clinical guidance. In the future, as functionalized detection technologies (e.g., AlphaCL) advance and become standardized, these biomarkers may become routine clinical tests, driving the transition of CSU management from empirical to precision medicine. This study bridges laboratory research and clinical practice, serving as a cornerstone for improving the overall care system for autoimmune skin diseases.
