Autoreactive T cells in chronic spontaneous urticaria target the IgE Fc receptor Ialpha subunit
- Author(s)
- Auyeung, P; Mittag, D; Hodgkin, PD; Harrison, LC;
- Journal Title
- Journal of Allergy and Clinical Immunology
- Publication Type
- Journal Article
- Abstract
- BACKGROUND: Chronic spontaneous urticaria (CSU) is the recurrence of urticaria without an apparent trigger. Half of the patients with CSU have IgG autoantibodies to FcepsilonRIalpha 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 FcepsilonRIalpha in patients with CSU and determine their relationship with autoantibodies to FcepsilonRIalpha and their diagnostic value. METHODS: T-cell responses to FcepsilonRIalpha were measured as proliferation by carboxy-fluorescein diacetate succinimidyl ester dye dilution and cytokine secretion by ELISpot. Serum autoantibodies to FcepsilonRIalpha were detected by radioimmunoprecipitation. RESULTS: Blood CD4+ T-cell proliferation to FcepsilonRIalpha was detected in 27% of the subjects with CSU and 0% of controls; IFN-gamma responses to FcepsilonRIalpha were detected in 53%, and IL-5 or IL-13 responses in a minority of subjects with CSU. Serum FcepsilonRIalpha autoantibodies were detected in 43% of subjects with CSU and 0% of controls. IFN-gamma and autoantibody responses to FcepsilonRIalpha were inversely related, with IFN-gamma responses being detected earlier than autoantibodies in disease. Combined with autoantibody, T-cell responses to FcepsilonRIalpha conferred high diagnostic sensitivity and specificity. CONCLUSIONS: Autoreactive CD4+ T cells that target FcepsilonRIalpha 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 FcepsilonRIalpha may signify different stages in the disease course. Our findings suggest that measurement of T-cell as well as autoantibody responses to FcepsilonRIalpha could improve diagnostic accuracy in subjects with CSU.
- Publisher
- Elsevier
- Research Division(s)
- Population Health And Immunity; Immunology
- PubMed ID
- 27417022
- Publisher's Version
- https://doi.org/10.1016/j.jaci.2016.04.036
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-08-10 04:12:49
Last Modified: 2018-07-11 09:38:57