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/jci200418838
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发表时间：
2004-05-01
影响因子：
15.9
通讯作者：
Roopenian, D
中科院分区：
文献类型：
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作者：
Akilesh, S;Petkova, S;Roopenian, D
MHC I类家族样Fc受体FcRn通常负责延长血清IgG Ab的寿命，但该分子是否参与自身免疫发病机制仍是推测性的。为了直接确定这一功能是否会导致不道德的自身免疫性疾病，我们在K/BxN小鼠模型中检测了FcRn重链缺陷是否会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袭性的遗传决定的K/BxN自身免疫性关节炎模型中给予部分或完全保护。FcRn缺乏的保护作用可能会被过量的致病性IgG Ab所覆盖。高剂量静脉注射IgG （IVIg）治疗FcRn饱和也能改善关节炎，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，连接了体液性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 Immoral 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.