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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Auyeung, Priscilla^1,2  Mittag, Diana^1,2,3  Hodgkin, Philip D.^1,2  Harrison, Leonard C.^1,2 

[1] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3010, Australia

[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia

[3] Acerta Pharma, Oss, Netherlands

关键词: Chronic spontaneous urticaria;    Fc epsilon RI alpha;    IgE;    autoantibody;    autoreactive T cell;    cytokine;    immune deviation;   

DOI  :  10.1016/j.jaci.2016.04.036

来源: Elsevier

【 摘 要 】

Background: Chronic spontaneous urticaria (CSU) is the recurrence of urticaria without an apparent trigger. Half of the patients with CSU have IgG autoantibodies to Fc epsilon RI alpha on dermal mast cells and basophils, which on activation release mediators responsible for urticaria. IgG autoantibodies infer the presence of antigen/disease-specific T cells and CSU lesions are characterized by T-cell infiltration, but antigen/disease-specific T cells have not been documented in patients with CSU. Objective: We aimed to identify autoreactive T cells to Fc epsilon RI alpha in patients with CSU and determine their relationship with autoantibodies to Fc epsilon RI alpha and their diagnostic value. Methods: T-cell responses to Fc epsilon RI alpha were measured as proliferation by carboxy-fluorescein diacetate succinimidyl ester dye dilution and cytokine secretion by ELISpot. Serum autoantibodies to Fc epsilon RI alpha were detected by radioimmunoprecipitation. Results: Blood CD4 1 T-cell proliferation to FceRIa was detected in 27% of the subjects with CSU and 0% of controls; IFN-gamma responses to Fc epsilon RI alpha were detected in 53%, and IL-5 or IL-13 responses in a minority of subjects with CSU. Serum FceRIa autoantibodies were detected in 43% of subjects with CSU and 0% of controls. IFN-gamma and autoantibody responses to Fc epsilon RI alpha were inversely related, with IFN-gamma responses being detected earlier than autoantibodies in disease. Combined with autoantibody, T-cell responses to Fc epsilon RI alpha conferred high diagnostic sensitivity and specificity. Conclusions: Autoreactive CD4 1 T cells that target Fc epsilon RI alpha were detected in most subjects with CSU, with a cytokine secretion profile more typical of a TH1-cell response. The inverse relationship between IFN-gamma and autoantibody responses to Fc epsilon RI alpha may signify different stages in the disease course. Our findings suggest that measurement of T-cell as well as autoantibody responses to Fc epsilon RI alpha could improve diagnostic accuracy in subjects with CSU.

【 授权许可】

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