GPIHBP1 autoantibody syndrome during interferon β1a treatment

Jun Eguchi, Kazuya Miyashita, Isamu Fukamachi, Katsuyuki Nakajima, Masami Murakami, Yuko Kawahara, Toru Yamashita, Yasuyuki Ohta, Koji Abe, Atsuko Nakatsuka, Mai Mino, Satoru Takase, Hiroaki Okazaki, Robert A. Hegele, Michael Ploug, Xuchen Hu, Jun Wada, Stephen G. Young, Anne P. Beigneux

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalJournal of Clinical Lipidology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Glycosylphosphatidylinositols
Autoantibodies
Interferons
Proteins
Lipoprotein Lipase
Therapeutics
Triglycerides
Capillary Action
Multiple Sclerosis
Reference Values
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • Autoantibodies
  • Chylomicronemia
  • GPIHBP1
  • Hypertriglyceridemia
  • Interferon β1a

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

Eguchi, J., Miyashita, K., Fukamachi, I., Nakajima, K., Murakami, M., Kawahara, Y., ... Beigneux, A. P. (Accepted/In press). GPIHBP1 autoantibody syndrome during interferon β1a treatment. Journal of Clinical Lipidology. https://doi.org/10.1016/j.jacl.2018.10.004

GPIHBP1 autoantibody syndrome during interferon β1a treatment. / Eguchi, Jun; Miyashita, Kazuya; Fukamachi, Isamu; Nakajima, Katsuyuki; Murakami, Masami; Kawahara, Yuko; Yamashita, Toru; Ohta, Yasuyuki; Abe, Koji; Nakatsuka, Atsuko; Mino, Mai; Takase, Satoru; Okazaki, Hiroaki; Hegele, Robert A.; Ploug, Michael; Hu, Xuchen; Wada, Jun; Young, Stephen G.; Beigneux, Anne P.

In: Journal of Clinical Lipidology, 01.01.2018.

Research output: Contribution to journalArticle

Eguchi, J, Miyashita, K, Fukamachi, I, Nakajima, K, Murakami, M, Kawahara, Y, Yamashita, T, Ohta, Y, Abe, K, Nakatsuka, A, Mino, M, Takase, S, Okazaki, H, Hegele, RA, Ploug, M, Hu, X, Wada, J, Young, SG & Beigneux, AP 2018, 'GPIHBP1 autoantibody syndrome during interferon β1a treatment', Journal of Clinical Lipidology. https://doi.org/10.1016/j.jacl.2018.10.004
Eguchi, Jun ; Miyashita, Kazuya ; Fukamachi, Isamu ; Nakajima, Katsuyuki ; Murakami, Masami ; Kawahara, Yuko ; Yamashita, Toru ; Ohta, Yasuyuki ; Abe, Koji ; Nakatsuka, Atsuko ; Mino, Mai ; Takase, Satoru ; Okazaki, Hiroaki ; Hegele, Robert A. ; Ploug, Michael ; Hu, Xuchen ; Wada, Jun ; Young, Stephen G. ; Beigneux, Anne P. / GPIHBP1 autoantibody syndrome during interferon β1a treatment. In: Journal of Clinical Lipidology. 2018.
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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.",
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AU - Eguchi, Jun

AU - Miyashita, Kazuya

AU - Fukamachi, Isamu

AU - Nakajima, Katsuyuki

AU - Murakami, Masami

AU - Kawahara, Yuko

AU - Yamashita, Toru

AU - Ohta, Yasuyuki

AU - Abe, Koji

AU - Nakatsuka, Atsuko

AU - Mino, Mai

AU - Takase, Satoru

AU - Okazaki, Hiroaki

AU - Hegele, Robert A.

AU - Ploug, Michael

AU - Hu, Xuchen

AU - Wada, Jun

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KW - Autoantibodies

KW - Chylomicronemia

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KW - Hypertriglyceridemia

KW - Interferon β1a

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