Xuchen Hu1, Geesje M Dallinga-Thie2, G Kees Hovingh2, Sandy Y Chang1, Norma P Sandoval1, Tiffany Ly P Dang1, Isamu Fukamachi3, Kazuya Miyashita4, Katsuyuki Nakajima5, Masami Murakami5, Loren G Fong1, Michael Ploug6, Stephen G Young7, Anne P Beigneux8. 1. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 2. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. 3. Immuno-Biological Laboratories (IBL) Co, Ltd, Fujioka, Gunma, Japan. 4. Immuno-Biological Laboratories (IBL) Co, Ltd, Fujioka, Gunma, Japan; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. 5. Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. 6. Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. 7. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: sgyoung@mednet.ucla.edu. 8. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: abeigneux@mednet.ucla.edu.
Abstract
BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 ("GPIHBP1 autoantibody syndrome"). OBJECTIVE: Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. METHODS: We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies. RESULTS: The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. CONCLUSIONS: One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment.
BACKGROUND:GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 ("GPIHBP1 autoantibody syndrome"). OBJECTIVE: Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. METHODS: We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies. RESULTS: The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. CONCLUSIONS: One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment.
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