Serum IgG autoantibodies directed against the a chain of Fc epsilon RI: A selective marker and pathogenetic factor for a distinct subset of chronic UrtiCaria patients?
Serum IgG autoantibodies directed against the a chain of Fc epsilon RI: A selective marker and pathogenetic factor for a distinct subset of chronic UrtiCaria patients?
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DOI：
10.1172/jci118325
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Stingl, G
中科院分区：
文献类型：
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作者：
Fiebiger, E;Maurer, D;Stingl, G
虽然众所周知，急性过敏性荨麻疹是由高亲和力 IgE 受体 (Fc epsilon RI) 过敏原/IgE 依赖性交联后发生的皮肤肥大细胞脱颗粒引起的，但慢性荨麻疹 (CU) 的病理生理机制尚不清楚。一些证据表明 CU 患者血清中存在组胺释放活性，可能通过触发 Fc epsilon RI 发挥作用。在本研究中，我们旨在使用亲和纯化的、IgE耗尽的 CU 患者的 IgG 级分 (CU-IgG) 更好地表征 CU 患者的这种抗 Fc epsilon RI α 反应性。使用固定化重组可溶性 Fc epsilon RI α 作为蛋白质印迹研究的反应靶标，我们发现 12/32 (37%) CU-IgG 血清样品表现出针对 Fc epsilon RI α 的 IgG 自身反应性。这些发现通过实验得到证实，证明免疫印迹反应性而非免疫印迹非反应性 CU-IgG 制剂从 Fc epsilon RI α γ 转染的细胞中沉淀出 Fc epsilon RI α，在来自特应性皮炎 (AD) 患者 (0/15) 或健康对照个体 (CO: 0/15) 的 IgG 级分中未观察到抗 Fc epsilon RI α 反应性，与选择性的CU 患者中出现 IgG 抗 Fc epsilon RI α 自身抗体，在所有研究组中均检测到 IgG 抗 IgE 抗体（CU：69%；AD：73%；CO：26%），虽然两种类型的自身抗体都可以表现出组胺释放特性，但并非所有自身抗体都被证明在体外具有功能。我们的结果表明 IgG 抗 Fc epsilon RI α 反应性的出现定义了CU 的自身免疫介导的亚实体，并为开发新的诊断程序以及可能的该疾病的治疗策略提供基础。
While it is well established that acute allergic urticaria is caused by degranulation of skin mast cells occurring after allergen/IgE-dependent cross-linking of high affinity IgE receptors (Fc epsilon RI), the pathophysiologic mechanisms operative in chronic urticaria (CU) are less well understood, Some evidence points to the existence of histamine-releasing activity in the serum of CU patients which possibly acts via triggering of Fc epsilon RI. In this study, we aimed to better characterize this anti-Fc epsilon RI alpha reactivity of CU patients using affinity-purified, IgE-depleted IgG fractions of such individuals (CU-IgG), Using immobilized, recombinant soluble Fc epsilon RI alpha as a reaction target for Western blot studies, we found that 12/32 (37%) CU-IgG serum samples exhibited IgG autoreactivity against Fc epsilon RI alpha. These findings were confirmed by experiments demonstrating that immunoblot-reactive, but not immunoblot-nonreactive, CU-IgG preparations precipitated the Fc epsilon RI alpha from Fc epsilon RI alpha gamma-transfected cells, No anti-Fc epsilon RI alpha reactivity was observed in IgG fractions from atopic dermatitis (AD) patients (0/15) or healthy control individuals (CO: 0/15), As opposed to the selective occurrence of IgG anti-Fc epsilon RI alpha autoantibodies in CU patients, IgG anti-IgE antibodies were detected in all groups investigated (CU: 69%; AD: 73%; CO: 26%), While both types of autoantibodies can exhibit histamine-releasing properties, not all of the autoantibodies proved to be functional in vitro, Our results indicate that the occurrence of IgG anti-Fc epsilon RI alpha reactivity defines an autoimmune-mediated subentity of CU and provide a basis for the development of new diagnostic procedures and, perhaps, therapeutic strategies for this disease.