CSL Behring AG, Bern, Switzerland.
Vox Sang. 2009 Nov;97(4):348-54. doi: 10.1111/j.1423-0410.2009.01217.x. Epub 2009 Jul 27.
Complement inhibition is considered important in the mechanism of action of intravenous immunoglobulin (IVIG) in a number of inflammatory and autoimmune disorders. The capacity of different IVIG preparations to 'scavenge' activated C3 and thereby inhibit complement activation was assessed by a new in vitro assay.
Diluted human serum as a complement source, with or without addition of different concentrations of IVIG, was incubated in microtitre plates coated with heat-aggregated human IgG. Complement scavenging was measured by detecting reduced C3 binding and determining fluid phase C3b-IgG complex formation. Complement activation induced by the IVIG preparations was measured as C5a formation.
All IVIG preparations exhibited a dose-dependent inhibition of C3b deposition, correlating strongly with binding of C3b to fluid-phase IgG, but the extent of complement scavenging varied considerably between different IVIG preparations. At an IVIG concentration of 0.9 mg/ml, the inhibition of C3b deposition ranged from 72 +/- 16% to 22 +/- 4.1%. The reduction of C3b deposition on the complement-activating surface was not due to IVIG-induced complement activation in the fluid phase, as shown by the low C5a formation in the presence of serum.
In vitro analysis allows comparison of the complement-inhibitory properties of IVIG preparations. The extent of complement scavenging varies between the products.
补体抑制被认为是静脉注射免疫球蛋白（IVIG）在多种炎症和自身免疫性疾病中的作用机制之一。通过一种新的体外测定方法评估了不同 IVIG 制剂“清除”活化 C3 的能力，从而抑制补体激活。
用或不用不同浓度的 IVIG 稀释的人血清作为补体来源，在涂有热聚集人 IgG 的微量滴定板中孵育。通过检测减少的 C3 结合和确定液相 C3b-IgG 复合物形成来测量补体清除。通过 C5a 形成测量 IVIG 制剂诱导的补体激活。
所有 IVIG 制剂均表现出剂量依赖性抑制 C3b 沉积，与 C3b 与液相 IgG 的结合密切相关，但不同 IVIG 制剂之间的补体清除程度差异很大。在 IVIG 浓度为 0.9 mg/ml 时，C3b 沉积的抑制范围为 72±16%至 22±4.1%。在血清存在的情况下，C3b 沉积的减少不是由于 IVIG 诱导的液相补体激活所致，因为 C5a 的形成很低。
体外分析允许比较 IVIG 制剂的补体抑制特性。产品之间的补体清除程度有所不同。
