title: Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma.
abstract: 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.
authors: From the Department of Medicine, Section of Hematology (S.N., A.R.B., C.S.B., M.V.D.), Section of Digestive Diseases (J.L., P.K.M.), Yale Liver Center (P.K.M.), and Yale Cancer Center (M.V.D.), Yale University School of Medicine, New Haven, CT.
authors: Shiny
authors: S
authors: Nair
authors: Andrew R
authors: AR
authors: Branagan
authors: Jun
authors: J
authors: Liu
authors: Chandra Sekhar
authors: CS
authors: Boddupalli
authors: Pramod K
authors: PK
authors: Mistry
authors: Madhav V
authors: MV
authors: Dhodapkar
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005776:Gaucher Disease / Q000150:complications / Q000276:immunology*; D005963:Glucosylceramides / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D008244:Lysophosphatidylcholines / Q000032:analysis / Q000276:immunology*; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology*
chemical_list: D005963:Glucosylceramides; D007136:Immunoglobulins; D008244:Lysophosphatidylcholines