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

Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.