Massive immune response against IVIg interferes with response against other antigens in mice: A new mode of action?
Massive immune response against IVIg interferes with response against other antigens in mice: A new mode of action?
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DOI：
10.1371/journal.pone.0186046
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发表时间：
2017-10-12
期刊：
影响因子：
3.7
通讯作者：
Karle, Anette
中科院分区：
文献类型：
--
作者：
Sorde, Laetitia;Spindeldreher, Sebastian;Karle, Anette
大剂量静脉注射免疫球蛋白（IVIg）是临床上广泛使用的治疗自身免疫性疾病和严重炎症性疾病的药物。然而，对其作用机制仍知之甚少。我们使用体内卵清蛋白（Ova）免疫小鼠模型评估了IVIg对免疫细胞群的影响。高剂量IVIg显著降低Ova特异性抗体应答。有趣的是，所获得的结果表明针对IVIg的立即和大量免疫反应，如脾和引流淋巴结中B细胞和CD4+ T细胞的活化和扩增以及IVIg特异性抗体的产生所示。我们建议，IVIg的竞争，在T细胞水平上的反应，对OVA解释免疫调节特性的IVIg。两种单克隆抗体没有成功地复制IVIg的效果。这表明，除了小鼠对人恒定结构域的反应，IVIg的巨大序列多样性可能显着有助于这种针对IVIg的大规模免疫应答。虽然这些发现与IVIg治疗患者的相关性仍有待探讨，但我们的数据首次证明IVIg将免疫应答重定向至IVIg，而远离特异性抗原应答。
Administration of high dose intravenous immunoglobulin (IVIg) is widely used in the clinic to treat autoimmune and severe inflammatory diseases. However, its mechanisms of action remain poorly understood. We assessed the impact of IVIg on immune cell populations using an in vivo ovalbumin (Ova)-immunization mouse model. High dose IVIg significantly reduced the Ova-specific antibody response. Intriguingly, the results obtained indicate an immediate and massive immune reaction against IVIg, as shown by the activation and expansion of B cells and CD4+ T cells in the spleen and draining lymph nodes and the production of IVIg-specific antibodies. We propose that IVIg competes at the T-cell level with the response against Ova to explain the immunomodulatory properties of IVIg. Two monoclonal antibodies did not succeeded in reproducing the effects of IVIg. This suggests that in addition to the mouse response against human constant domains, the enormous sequence diversity of IVIg may significantly contribute to this massive immune response against IVIg. While correlation of these findings to IVIg-treated patients remains to be explored, our data demonstrate for the first time that IVIg re-directs the immune response towards IVIg and away from a specific antigen response.