Purpose: Immunoglobulin (Ig) E autoantibodies against thyroid antigens such as thyroid peroxidase (TPO) have been demonstrated in chronic spontaneous urticaria (CSU) patients in higher frequency than healthy subjects.However, if these IgE autoantibodies can trigger urticaria is still a matter of study.The aim of this study was to investigate the relationship between concomitant IgE autoantibodies against thyroid antigens in CSU.Methods: Patients with CSU, healthy subjects and patients with autoimmune thyroid disease (ATD) were recruited.Total IgE and specific anti-TPO IgE and IgG were assessed in all subjects.The basophil activation test and skin tests with TPO were performed to demonstrate whether this antigen could selectively induce urticaria reaction in subjects with positive anti-TPO IgE.Results: Anti-TPO IgE was present in all 3 groups (CSU: 34.0%, ATD: 16.6%, healthy subjects: 8.1%).Anti-TPO IgE levels were higher in CSU patients, whereas anti-TPO IgG were higher in ATD patients.After exposure to TPO, CD203c expression from patients with CSU and anti-TPO IgE significantly increased in comparison to the other groups; 33.0% vs. 14.0% in ATD patients and 9.0% in control subjects (P < 0.05).Skin reactions with TPO were higher in patients with CSU according to the intradermal (CSU: 18.0%, ATD: 3.3%, control: 8.0%) and skin prick tests (12.0%, 0%, 0%, respectively).Passive transfer of anti-TPO IgE from a CSU patient to the skin of control subjects without anti-TPO IgE induced a positive skin reaction.Conclusions: Anti-TPO IgE is not a specific biomarker for CSU.However, IgE against TPO plays a pathogenic role in inducing effector cell activation and skin exacerbation in some patients with CSU.