The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease.
The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease.
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DOI：
10.1172/jci18838
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发表时间：
2004-05
期刊：
影响因子：
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通讯作者：
S. Akilesh;Stefka B. Petkova;T. Sproule;D. Shaffer;G. Christianson;D. Roopenian
中科院分区：
文献类型：
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作者：
S. Akilesh;Stefka B. Petkova;T. Sproule;D. Shaffer;G. Christianson;D. Roopenian
MHC I类家族样Fc受体FcRn通常负责延长血清IgG Ab的寿命，但该分子是否有助于自身免疫发病机制仍然是推测性的。为了直接确定这种功能是否有助于体液自身免疫性疾病，我们在K/BxN小鼠模型中检查了FcRn重链的缺陷是否影响自身免疫性关节炎。FcRn缺乏在致关节炎血清转移和更具侵略性的遗传决定的K/BxN自身免疫性关节炎模型中提供部分或完全保护。FcRn缺乏的保护作用可能会被过量的致病性IgG Ab所抵消。高剂量静脉注射IgG（IVIg）对FcRn的治疗饱和也改善了关节炎，直接暗示FcRn阻断是IVIg抗炎作用的重要机制。结果表明，FcRn是一个潜在的治疗靶点，连接体液自身免疫性疾病的起始和效应阶段。
The MHC class I family-like Fc receptor, FcRn, is normally responsible for extending the life span of serum IgG Ab's, but whether this molecule contributes to autoimmune pathogenesis remains speculative. To determine directly whether this function contributes to humoral autoimmune disease, we examined whether a deficiency in the FcRn heavy chain influences autoimmune arthritis in the K/BxN mouse model. FcRn deficiency conferred either partial or complete protection in the arthritogenic serum transfer and the more aggressive genetically determined K/BxN autoimmune arthritis models. The protective effects of an FcRn deficiency could be overridden with excessive amounts of pathogenic IgG Ab's. The therapeutic saturation of FcRn by high-dose intravenous IgG (IVIg) also ameliorated arthritis, directly implicating FcRn blockade as a significant mechanism of IVIg's anti-inflammatory action. The results suggest that FcRn is a potential therapeutic target that links the initiation and effector phases of humoral autoimmune disease.