Differential associations of IgG-aFcεRI and IgG-aIgE autoantibodies with clinical phenotypes of type IIb chronic spontaneous urticaria

<h2>Abstract</h2><h3>Background</h3> Chronic spontaneous urticaria (CSU) is a common mast cell-driven skin disorder characterized by recurrent wheals and/or angioedema lasting more than 6 weeks. A subset of patients shows type IIb autoimmune features, including IgG autoantibodies against FcεRI or IgE, which have been associated with more severe and treatment-refractory disease. <h3>Objective</h3> This study aimed to explore the associations of IgG-aFcεRI and IgG-aIgE autoantibodies with clinical and laboratory features of CSU and to assess whether these autoantibody patterns are linked to distinct clinical phenotypes. <h3>Methods</h3> Adult patients with CSU underwent standardized clinical evaluation and completed validated patient-reported outcome measures (UCT, UAS7, CU-Q2oL, AECT, AAS, AE-QoL, and VAS). Venous blood samples were collected and analyzed for HSP70, anti-HSP70, and IgG autoantibodies against FcεRI and IgE using ELISA. Additional laboratory data were obtained from the national DataMed system. Statistical analyses were performed using Jamovi v2.7.5, with p < 0.05 considered statistically significant. <h3>Results</h3> The study included 205 adults (77.6% female; mean age 42.8 years), of whom 199 were tested for IgG-aFcεRI and IgG-aIgE. Higher IgG-aIgE levels were observed in patients with angioedema (either angioedema alone or urticaria with angioedema), as well as in those reporting accompanying symptoms, receiving omalizumab treatment, living in rural areas, and experiencing predominantly nighttime symptoms. In contrast, higher IgG-aFcεRI levels were associated with wheal-predominant disease and anti-TPO positivity. IgG-aFcεRI levels correlated negatively with IgG-aIgE, neutrophil count, and total IgE, and positively with total IgG. <h3>Conclusion</h3> Higher IgG-aIgE levels were associated with angioedema, accompanying symptoms, omalizumab use, rural residence, and nighttime symptom patterns, suggesting an association with distinct clinical features of CSU. In contrast, higher IgG-aFcεRI levels were associated with wheal-predominant disease and anti-TPO positivity.