Since the first description of the administration of high doses of pooled serum IgG, also referred to as intravenous IgG (IVIg) therapy, as being able to ameliorate various autoimmune diseases, researchers have been investigating which molecular and cellular pathways underlie IVIg activity. Apart from trying to understand the obvious conundrum that IgG can trigger both autoimmune pathology and resolution of inflammation, the rapidly expanding use of IVIg has led to a lack of availability of this primary blood product, providing a strong rationale for developing recombinant alternatives. During the last decade, a tremendous number of novel insights into IVIg activity brought the goal of replacing IVIg within reach, at least in select indications, and has led to the initiation of several clinical trials. At the forefront of this effort is the modulation of autoantibody half-life and blocking access of autoantibodies to fragment cystallizable γ receptors (Fcγ receptors). In this rostrum article, we will briefly discuss current models of IVIg activity, followed by a more specific focus on novel therapeutic avenues that are entering the clinic and may replace IVIg in the future.

自从首次对高剂量合并血清IgG（也称为静脉IgG（IVIg）治疗）的给药进行描述以来，由于能够缓解各种自身免疫性疾病，研究人员一直在研究IVIg活性的分子和细胞途径。除了试图了解IgG可以触发自身免疫病理学和炎症消退的明显难题之外，IVIg的迅速扩展使用还导致该初级血液产品的可用性不足，为开发重组替代品提供了强有力的理由。在过去的十年中，对IVIg活性的大量新颖见解使至少在某些适应症中达到替代IVIg的目标成为现实，并导致了数项临床试验的启动。这项工作的最前沿是调节自身抗体的半衰期并阻止自身抗体进入片段化可囊化的γ受体（Fcγ受体）。在这篇讲台文章中，我们将简要讨论IVIg活性的当前模型，然后更具体地关注进入临床并可能在将来替代IVIg的新型治疗途径。