[HTML][HTML] Clonal immunoglobulin against lysolipids in the origin of myeloma

S Nair, AR Branagan, J Liu… - … England Journal of …, 2016 - Mass Medical Soc
New England Journal of Medicine, 2016Mass Medical Soc
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 …
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, long-term immune activation by lysolipids may underlie both Gaucher’s disease–associated gammopathies and some sporadic monoclonal gammopathies.
The New England Journal Of Medicine