Walter and Eliza Hall Institute of Medical Research and the Department of Medical Biology, University of Melbourne, Melbourne, Australia.
Walter and Eliza Hall Institute of Medical Research and the Department of Medical Biology, University of Melbourne, Melbourne, Australia.
J Allergy Clin Immunol. 2016 Sep;138(3):761-768.e4. doi: 10.1016/j.jaci.2016.04.036. Epub 2016 Jun 8.
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 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.
We aimed to identify autoreactive T cells 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(+) T cells 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.
慢性自发性荨麻疹（CSU）是指无明显诱因的荨麻疹反复发作。CSU 患者中有一半的人真皮肥大细胞和嗜碱性粒细胞上存在针对 FcεRIα 的 IgG 自身抗体，这些自身抗体在被激活后会释放导致荨麻疹的介质。IgG 自身抗体提示存在抗原/疾病特异性 T 细胞，CSU 病变的特征是 T 细胞浸润，但尚未在 CSU 患者中记录到抗原/疾病特异性 T 细胞。
我们旨在鉴定 CSU 患者中针对 FcεRIα 的自身反应性 T 细胞，并确定其与针对 FcεRIα 的自身抗体的关系及其诊断价值。
通过羧基荧光素二乙酸琥珀酰亚胺酯染料稀释法测量 T 细胞对 FcεRIα 的增殖反应，并通过 ELISpot 测量细胞因子分泌。通过放射免疫沉淀法检测血清针对 FcεRIα 的自身抗体。
在 27%的 CSU 患者和 0%的对照组中检测到针对 FcεRIα 的血液 CD4(+) T 细胞增殖；在 53%的 CSU 患者和少数患者中检测到针对 FcεRIα 的 IFN-γ 反应，而 IL-5 或 IL-13 反应。在 43%的 CSU 患者和 0%的对照组中检测到针对 FcεRIα 的血清自身抗体。针对 FcεRIα 的 IFN-γ 和自身抗体反应呈负相关，IFN-γ 反应在疾病中比自身抗体更早出现。与自身抗体结合，针对 FcεRIα 的 T 细胞反应具有较高的诊断敏感性和特异性。
在大多数 CSU 患者中检测到针对 FcεRIα 的自身反应性 CD4(+) T 细胞，其细胞因子分泌谱更典型的是 TH1 细胞反应。IFN-γ 与针对 FcεRIα 的自身抗体反应之间的负相关可能表明疾病过程中的不同阶段。我们的研究结果表明，测量针对 FcεRIα 的 T 细胞和自身抗体反应可能会提高 CSU 患者的诊断准确性。
