Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy.
UOC Dermatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Clin Exp Immunol. 2020 Jun;200(3):242-249. doi: 10.1111/cei.13428. Epub 2020 Mar 17.
Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.
慢性自发性荨麻疹（CSU）的发病机制显示出免疫球蛋白（Ig）G 和 IgE 介导的自身免疫之间复杂且仍不清楚的相互作用，导致肥大细胞和嗜碱性粒细胞脱颗粒和风团形成。本研究的目的是同时评估 CSU 患者对公认和最近报道的自身抗原的 IgE 和 IgG 反应性，并评估这种反应性对抗 IgE 单克隆抗体奥马珠单抗的反应的影响。20 名 CSU 患者接受奥马珠单抗治疗。在基线和不同的药物给药时间点记录荨麻疹活动评分 7（UAS7），以将早期、晚期或无反应者进行分类。在基线时，通过免疫酶方法检测 20 名患者和 20 名对照者的血清中高亲和力和低亲和力 IgE 受体（FcεRI 和 FcεRII）、组织因子（TF）和甲状腺球蛋白（TG）的 IgE 和 IgG 自身抗体。将抗体水平与对照组进行比较，并根据反应进行分析。18 名患者是奥马珠单抗的应答者（11 名早期应答者和 7 名晚期应答者），而 2 名患者是无应答者。超过 50%的患者同时具有至少一种四种不同自身抗原的 IgE 和 IgG 自身抗体。晚期应答者的抗 TF IgE 和 IgG 水平均高于早期应答者（P = 0.011 和 P = 0.035）。25%的患者具有超过正常上限的抗 FcεRI IgE 水平，提示其可能是 CSU 的一种新型自身过敏原。在 CSU 中，存在一种自身免疫环境，其特征是相同抗原/过敏原的 IgE 和 IgG 自身抗体共存，特别是在奥马珠单抗的晚期应答者中，这可能解释了较慢的反应。
