• Anne P Beigneux, Kazuya Miyashita, Michael Ploug, Dirk J Blom, Masumi Ai, MacRae F Linton, Weerapan Khovidhunkit, Robert Dufour, Abhimanyu Garg, Maureen A McMahon, Clive R Pullinger, Norma P Sandoval, Xuchen Hu, Christopher M Allan, Mikael Larsson, Tetsuo Machida, Masami Murakami, Karen Reue, Peter Tontonoz, Ira J Goldberg, Philippe Moulin, Sybil Charrière, Loren G Fong, Katsuyuki Nakajima, and Stephen G Young.
• 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 Cardiovascular Research Institute and Department of Physiological Nursing, University of California, San Francisco, San Francisco (C.R.P.); the Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi (K.M., T.M., M.M., K.N.), and the Department of Insured Medical Care Management, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (M.A.) - both in Japan; the Finsen Laboratory, Rigshospitalet, Copenhagen (M.P.); the Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); the Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville (M.F.L.); the Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Society, Bangkok, Thailand (W.K.); Clinique de Prévention Cardiovasculaire, Institut de Recherches Cliniques de Montréal, University of Montreal, Montreal (R.D.); the Department of Medicine, University of Texas Southwestern Medical Center, Dallas (A.G.); the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York (I.J.G.); and Fédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, INSERM UMR-1060 Carmen, Université de Lyon, Lyon, France (P.M., S.C.).
• N. Engl. J. Med. 2017 Apr 27; 376 (17): 1647-1658.

BackgroundA 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.MethodsUsing 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.ResultsWe 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.ConclusionsIn 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.).

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