Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma.
Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma.
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DOI：
10.1056/nejmoa1508808
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发表时间：
2016-02-11
期刊：
影响因子：
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通讯作者：
Dhodapkar MV
中科院分区：
文献类型：
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作者：
Nair S;Branagan AR;Liu J;Boddupalli CS;Mistry PK;Dhodapkar MV
抗原驱动的选择已被牵连在单克隆丙种球蛋白病的发病机制。戈谢病患者发生单克隆丙种球蛋白病的风险增加。在这里，我们表明，高雪氏病患者和高雪氏病相关丙种球蛋白病小鼠模型中的克隆免疫球蛋白对溶血葡萄糖神经酰胺（LGL1）有反应，而LGL1在这些患者和小鼠中明显升高。33%的散发性人单克隆丙种球蛋白病中的克隆免疫球蛋白也对溶血脂质LGL1和溶血磷脂酰胆碱（LPC）具有特异性。底物减少改善小鼠高雪氏病相关丙种球蛋白病因此，溶血脂质的长期免疫激活可能是戈谢病相关丙种球蛋白病和一些散发性单克隆丙种球蛋白病的基础。
Antigen-driven selection has been implicated in the pathogenesis of monoclonal gammopathies. Patients with Gaucher’s disease have an increased risk of monoclonal gammopathies. Here we show that the clonal immunoglobulin in patients with Gaucher’s disease and in mouse models of Gaucher’s disease–associated gammopathy is reactive against lyso-glucosylceramide (LGL1), which is markedly elevated in these patients and mice. Clonal immunoglobulin in 33% of sporadic human monoclonal gammopathies is also specific for the lysolipids LGL1 and lysophosphatidylcholine (LPC). Substrate reduction ameliorates Gaucher’s disease–associated gammopathy in mice. Thus, longterm immune activation by lysolipids may underlie both Gaucher’s disease–associated gammopathies and some sporadic monoclonal gammopathies.