Jun Eguchi1, Kazuya Miyashita2, Isamu Fukamachi3, Katsuyuki Nakajima4, Masami Murakami4, Yuko Kawahara5, Toru Yamashita5, Yasuyuki Ohta5, Koji Abe5, Atsuko Nakatsuka1, Mai Mino1, Satoru Takase6, Hiroaki Okazaki6, Robert A Hegele7, Michael Ploug8, Xuchen Hu9, Jun Wada10, Stephen G Young11, Anne P Beigneux12. 1. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. 2. Immuno-Biological Laboratories (IBL) Co., Ltd., Fujioka, Gunma, Japan; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. 3. Immuno-Biological Laboratories (IBL) Co., Ltd., Fujioka, Gunma, Japan. 4. Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. 5. Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. 6. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 7. Department of Medicine and Robarts Research Institute, Western University, London, Ontario, Canada. 8. Finsen Laboratory, Rigshospitalet, Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N, Denmark. 9. Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. 10. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. Electronic address: junwada@okayama-u.ac.jp. 11. Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Departments of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: sgyoung@mednet.ucla.edu. 12. Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: abeigneux@mednet.ucla.edu.
Abstract
BACKGROUND: Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen. OBJECTIVE: A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies. METHODS: We tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells. RESULTS: During IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable. CONCLUSION: The appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.
BACKGROUND: Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen. OBJECTIVE: A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies. METHODS: We tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells. RESULTS: During IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable. CONCLUSION: The appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.
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