AUTOANTIBODIES AGAINST THE HIGH-AFFINITY IGE RECEPTOR AS A CAUSE OF HISTAMINE-RELEASE IN CHRONIC URTICARIA
AUTOANTIBODIES AGAINST THE HIGH-AFFINITY IGE RECEPTOR AS A CAUSE OF HISTAMINE-RELEASE IN CHRONIC URTICARIA
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DOI：
10.1056/nejm199306033282204
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发表时间：
1993-06-03
影响因子：
158.5
通讯作者：
GREAVES, MW
中科院分区：
文献类型：
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作者：
HIDE, M;FRANCIS, DM;GREAVES, MW
背景资料。大多数荨麻疹是由肥大细胞释放的组胺等血管活性介质引起的。虽然肥大细胞通过细胞表面结合的IgE的交联被变应原激活，但这一机制似乎不能解释大多数慢性荨麻疹病例，当过敏、感染、药物诱导或物理原因无法确定时，这些病例被归类为特发性。我们招募了26名慢性特发性荨麻疹患者，皮内注射自体血清引起风团和红斑反应。研究了4例血清IgE水平极低的供者嗜碱性粒细胞显著释放组胺的血清对组胺释放的IgE依赖性、免疫球蛋白G组分的活性以及重组重组制剂(SFcepsilonRIpha)的中和作用。嗜碱性粒细胞对骨髓瘤IgE被动致敏后，血清组胺释放活性被取消，用乳酸处理解离IgE后，血清组胺释放活性增强，并被所有4例患者血清中的免疫球蛋白G组分诱导。血清和分离的免疫球蛋白与sFcepsilonRIpha预孵育后，几乎完全中和。抗高亲和力IgE受体α亚基的组胺释放免疫球蛋白自身抗体存在于一些慢性荨麻疹患者的循环中。自身抗体诱导的IgE受体交联化可能是肥大细胞介导的慢性荨麻疹等疾病发病的重要机制。
Background. Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface-bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic.Methods. We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the a subunit of the high-affinity IgE receptor (sFcepsilonRIalpha).Results. The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFcepsilonRIalpha resulted in almost complete neutralization.Conclusions. Histamine-releasing IgG autoantibodies against the a subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.