Ferrer M, Nakazawa K, Kaplan A P
Asthma and Allergy Center, Division of Pulmonary Diseases, Department of Medicine, Medical University of South Carolina, Charleston, USA.
J Allergy Clin Immunol. 1999 Jul;104(1):169-72. doi: 10.1016/s0091-6749(99)70129-6.
IgG autoantibodies directed to the alpha-subunit of the IgE receptor have been identified in 30% to 45% of patients with chronic urticaria. However, the exact mechanism by which histamine secretion is initiated is uncertain.
Histamine release from cutaneous mast cells may occur by cross-linking the IgE receptor or by activation of complement. Our goal is to distinguish these 2 possibilities.
We incubated human cutaneous mast cells with patient sera, decomplemented sera, or purified patient IgG. The IgG was also added to pooled normal serum or to sera deficient in either C2 or C5, and its ability to activate mast cells was assessed. Mast cells were incubated with human IgE myeloma to saturate alpha-subunits to determine the effect on histamine release.
Patient sera released histamine (18.26% +/- 4.39%), but purified IgG from patients (5.5% +/- 4.3%) did not. Addition of the patient IgG to normal sera rendered the sera positive for histamine-releasing activity (18.4% +/- 4.3%), whereas control IgG or patient IgG added to C2- or C5-deficient sera did not release histamine. Histamine release with decomplemented patient sera was also diminished (8.34% +/- 4.3%). Preincubation of mast cells with a C5-blocking peptide decreased histamine release but was not statistically significant; there was a significant decrease after preincubating mast cells with IgE myeloma.
The degranulation of mast cells by IgG autoantibodies in patients with chronic urticaria requires binding to the IgE receptor and activation of the classical complement cascade. Saturation of the IgE receptor with IgE inhibits such degranulation, presumably by preventing binding of the requisite IgG.
在30%至45%的慢性荨麻疹患者中已鉴定出针对IgE受体α亚基的IgG自身抗体。然而，组胺分泌起始的确切机制尚不确定。
皮肤肥大细胞释放组胺可能通过IgE受体交联或补体激活发生。我们的目标是区分这两种可能性。
我们将人皮肤肥大细胞与患者血清、去补体血清或纯化的患者IgG一起孵育。还将IgG添加到混合的正常血清或缺乏C2或C5的血清中，并评估其激活肥大细胞的能力。将肥大细胞与人IgE骨髓瘤一起孵育以饱和α亚基，以确定对组胺释放的影响。
患者血清释放组胺（18.26%±4.39%），但患者纯化的IgG（5.5%±4.3%）未释放。将患者IgG添加到正常血清中使血清组胺释放活性呈阳性（18.4%±4.3%），而添加到缺乏C2或C5的血清中的对照IgG或患者IgG未释放组胺。去补体的患者血清的组胺释放也减少（8.34%±4.3%）。用C5阻断肽预孵育肥大细胞可减少组胺释放，但无统计学意义；用IgE骨髓瘤预孵育肥大细胞后有显著减少。
慢性荨麻疹患者中IgG自身抗体引起的肥大细胞脱颗粒需要与IgE受体结合并激活经典补体级联反应。用IgE饱和IgE受体可抑制这种脱颗粒，推测是通过阻止必需IgG的结合。
