Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria

Abstract Background Chronic urticaria ( CU ) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, Fcε RI , and the therapeutic efficacy of anti‐IgE antibodies imply that IgE‐mediated mechanisms also play an important role in CU . Methods Reactivity of CU patients’ peripheral blood basophils (n=60) to specific anti‐Fcε RI and IgE‐independent fMLP stimulation was determined by basophil activation test in comparison with patients suffering from IgE‐mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (Fcε RI , Fcγ RII ) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria‐related symptoms were assessed by both UCT and CU ‐Q 2 oL. Results Stimulating CU patients’ basophils via Fcε RI , we identified three distinct immunologic phenotypes. One subgroup of patients’ basophils reacted to Fcε RI stimulation, whereas the others had anti‐Fcε RI nonreactive basophils. Among the latter, a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum‐induced basophil activation, increased levels of autoantibodies against thyroid peroxidase, and also exhibited the strongest disease impact on their quality of life. Conclusions Patients with CU can be categorized into three immunologic subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.