Autoreactive T cells in chronic spontaneous urticaria target the IgE Fc receptor Iα subunit

Abstract

Chronic spontaneous urticaria (CSU) is the recurrence of urticaria without an apparent trigger. Half of the patients with CSU have IgG autoantibodies to FcεRIα on dermal mast cells and basophils, which on activation release mediators responsible for urticaria. IgG autoantibodies infer the presence of antigen/disease-specific Tcells and CSU lesions are characterized by T-cell infiltration, but antigen/disease-specific Tcells have not been documented in patients with CSU. We aimed to identify autoreactive Tcells to FcεRIα in patients with CSU and determine their relationship with autoantibodies to FcεRIα and their diagnostic value. T-cell responses to FcεRIα were measured as proliferation by carboxy-fluorescein diacetate succinimidyl ester dye dilution and cytokine secretion by ELISpot. Serum autoantibodies to FcεRIα were detected by radioimmunoprecipitation. Blood CD4(+) T-cell proliferation to FcεRIα was detected in 27% of the subjects with CSU and 0% of controls; IFN-γ responses to FcεRIα were detected in 53%, and IL-5 or IL-13 responses in a minority of subjects with CSU. Serum FcεRIα autoantibodies were detected in 43% of subjects with CSU and 0% of controls. IFN-γ and autoantibody responses to FcεRIα were inversely related, with IFN-γ responses being detected earlier than autoantibodies in disease. Combined with autoantibody, T-cell responses to FcεRIα conferred high diagnostic sensitivity and specificity. Autoreactive CD4(+) Tcells that target FcεRIα were detected in most subjects with CSU, with a cytokine secretion profile more typical of a TH1-cell response. The inverse relationship between IFN-γ and autoantibody responses to FcεRIα may signify different stages in the disease course. Our findings suggest that measurement of T-cell as well as autoantibody responses to FcεRIα could improve diagnostic accuracy in subjects with CSU.