The role of FcγRIIA and IIIA polymorphisms in autoimmune diseases
The role of FcγRIIA and IIIA polymorphisms in autoimmune diseases
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DOI：
10.1016/j.biopha.2004.04.004
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发表时间：
2004-06-01
影响因子：
7.5
通讯作者：
Ioannidis, JPA
中科院分区：
文献类型：
--
作者：
Karassa, FB;Trikalinos, TA;Ioannidis, JPA
在过去的几年中，我们对人类Fc受体IgG （FcgammaR）的作用的了解已经大大增加。这些受体对IgG的亲和力、对IgG亚类的偏好、细胞类型特异性表达模式以及它们引发的细胞内信号各不相同。额外的FcgammaR异质性是由存在良好表征的遗传多态性引入的。fgammar基因的等位变异可能影响吞噬细胞的生物活性，为遗传易感性提供了基础。最近的证据表明，某些FcgammaR等位基因是系统性自身免疫性疾病及其主要表现发展的遗传危险因素。fcgammaria - r /H131多态性是系统性红斑狼疮（SLE）和抗磷脂综合征（APS）易感性的重要决定因素。低结合IgG2等位基因fcgammaria - r131似乎在隐性模型下赋予APS风险，而其对SLE易感性的影响可能具有剂量-反应特征。在欧洲血统的受试者中，由R131等位基因引起的狼疮病例的人群归因比例为13%，APS病例至少为10%。fgammariia - v /F158多态性对狼疮患者肾脏受累有显著影响。肾炎病例中可归因于低结合IgG I和IgG3 F158等位基因的比例约为10-14%。包括大量研究在内的荟萃分析已经很好地记录了这些遗传关联。除了流行病学和病理生理学方面的兴趣，这些知识可能在未来设计新的治疗干预措施中使用。(C) 2004年由Elsevier SAS出版。
Our knowledge about the role of human Fc receptors for IgG (FcgammaR) has increased considerably within the last several years. These receptors vary in their affinity for IgG, their preferences for IgG subclasses, the cell type-specific expression patterns, and the intracellular signals that they elicit. Additional FcgammaR heterogeneity is introduced by the presence of well characterized genetic polymorphisms. Allelic variants of FcgammaR genes may influence phagocyte biologic activity, providing a basis for inherited predisposition to disease. Recent evidence suggests that certain FcgammaR alleles are genetic risk factors for systemic autoimmune diseases and the development of major manifestations of these diseases. The FcgammaRIIA-R/H131 polymorphism is an important determinant of predisposition to systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). FcgammaRIIA-R131, the low-binding IgG2 allele, seems to confer risk for APS under a recessive model, whereas its effect on SLE susceptibility probably has a dose-response character. The population-attributable fraction of lupus cases due to the R131 allele is 13% and for APS cases is at least 10%, in subjects of European descent. The FcgammaRIIIA-V/F158 polymorphism has a significant impact on renal involvement in lupus patients. The proportion of nephritis cases that could be attributed to the low-binding IgG I and IgG3 F158 allele is approximately 10-14%. These genetic associations have been well documented in meta-analyses including a large number of studies. Besides the epidemiologic and pathophysiologic interest, this knowledge may be of use in the future in designing novel therapeutic interventions. (C) 2004 Published by Elsevier SAS.