Your browser doesn't support javascript.
loading
Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.
Beigneux, Anne P; Miyashita, Kazuya; Ploug, Michael; Blom, Dirk J; Ai, Masumi; Linton, MacRae F; Khovidhunkit, Weerapan; Dufour, Robert; Garg, Abhimanyu; McMahon, Maureen A; Pullinger, Clive R; Sandoval, Norma P; Hu, Xuchen; Allan, Christopher M; Larsson, Mikael; Machida, Tetsuo; Murakami, Masami; Reue, Karen; Tontonoz, Peter; Goldberg, Ira J; Moulin, Philippe; Charrière, Sybil; Fong, Loren G; Nakajima, Katsuyuki; Young, Stephen G.
Afiliação
  • Beigneux AP; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Miyashita K; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Ploug M; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Blom DJ; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Ai M; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Linton MF; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Khovidhunkit W; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Dufour R; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Garg A; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • McMahon MA; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Pullinger CR; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Sandoval NP; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Hu X; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Allan CM; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Larsson M; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Machida T; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Murakami M; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Reue K; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Tontonoz P; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Goldberg IJ; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Moulin P; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Charrière S; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Fong LG; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Nakajima K; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
  • Young SG; From the Departments of Medicine (A.P.B., M.A.M., N.P.S., X.H., C.M.A., M.L., L.G.F., S.G.Y.), Rheumatology (M.A.M.), Human Genetics (K.R., S.G.Y.), and Pathology and Laboratory Medicine (P.T.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, and the Cardiovascul
N Engl J Med ; 376(17): 1647-1658, 2017 04 27.
Article em En | MEDLINE | ID: mdl-28402248
ABSTRACT

BACKGROUND:

A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma samples (both from patients with chylomicronemia) that contained an interfering substance that made it impossible to measure GPIHBP1. That finding raised the possibility that those samples might contain GPIHBP1 autoantibodies.

METHODS:

Using a combination of immunoassays, Western blot analyses, and immunocytochemical studies, we tested the two plasma samples (as well as samples from other patients with chylomicronemia) for the presence of GPIHBP1 autoantibodies. We also tested the ability of GPIHBP1 autoantibodies to block the binding of lipoprotein lipase to GPIHBP1.

RESULTS:

We identified GPIHBP1 autoantibodies in six patients with chylomicronemia and found that these autoantibodies blocked the binding of lipoprotein lipase to GPIHBP1. As in patients with GPIHBP1 deficiency, those with GPIHBP1 autoantibodies had low plasma levels of lipoprotein lipase. Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1 autoantibodies had a response to treatment with immunosuppressive agents.

CONCLUSIONS:

In six patients with chylomicronemia, GPIHBP1 autoantibodies blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby interfering with lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.).
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Receptores de Lipoproteínas / Lipase Lipoproteica / Hiperlipoproteinemia Tipo I Tipo de estudo: Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Receptores de Lipoproteínas / Lipase Lipoproteica / Hiperlipoproteinemia Tipo I Tipo de estudo: Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2017 Tipo de documento: Article