Advances in the understanding of the mechanism of action of IVIg
Advances in the understanding of the mechanism of action of IVIg
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DOI：
10.1007/s00415-008-3002-0
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发表时间：
2008-07-01
影响因子：
6
通讯作者：
Hartung, Hans-Peter
中科院分区：
文献类型：
--
作者：
Hartung, Hans-Peter
IgG分子是IVIg的主要成分。 IVIg 的商业制剂源自供体库，随后，IVIg 产品含有少量的 IgA 和 IgM 抗体以及 Th2 细胞因子和细胞因子拮抗剂，这些也可能有助于治疗效果。 IVIg 的众多靶点包括：T 细胞、细胞因子、免疫细胞运输、B 细胞、补体和 Fc 受体。 IVIg 已被证明可以通过竞争并中断自身反应性 T 细胞与抗原呈递细胞的相互作用来灭活它们。 IVIg 似乎也可以恢复细胞因子的平衡，研究表明 IVIg 含有促炎细胞因子的抗体和拮抗剂。此外，IVIg 被认为可以干扰并阻止自身免疫 T 细胞进入血神经屏障。外源抗体对 B 细胞的影响已得到充分研究； IVIg 被认为可以下调 B 细胞的抗体产生，通过阻断细胞表面受体干扰 B 细胞增殖，并防止 B 细胞某些亚型的激活。此外，IVIg 可以通过中断补体激活级联中的步骤并阻断 Fc 受体介导的活性来影响先天免疫，从而导致巨噬细胞活性下调。总之，IVIg 有多种作用模式，最终导致免疫反应下调；其中许多可能与神经肌肉疾病和免疫神经病有关。
The IgG molecule is the main component of IVIg. Commercial preparations of IVIg are derived from a pool of donors and subsequently, IVIg products contain smaller amounts of IgA and IgM antibodies as well as Th2 cytokines and cytokine antagonists that may also contribute to therapeutic effects. Numerous targets for IVIg include: T-cells, cytokines, immune cell trafficking, B-cells, complement and Fc-receptors. IVIg has been demonstrated to inactivate auto-reactive T-cells by competing for and interrupting their interaction with antigen presenting cells. The balance of cytokines also appears to be restored by IVIg, with studies showing that IVIg contains antibodies and antagonists to pro-inflammatory cytokines. in addition, IVIg is thought to interfere with and prevent the passage of auto-immune T-cells into the blood-nerve barrier. The effects of exogenous antibodies on B-cells have been well studied; IVIg is thought to down-regulate anti-body production by B-cells, interfere with B-cell proliferation via a blockade of cell surface receptors and prevent the activation of certain subtypes of B-cell. In addition, IVIg can affect innate immunity by interrupting the steps in the complement activation cascade and blocking Fc-receptor mediated activity, which results in down-regulation of macrophage activity. In conclusion, IVIg has numerous modes of action, which culminate in the down-regulation of the immune response; many of which may be relevant to neuromuscular disorders and immune neuropathies.