PMID- 32948662 OWN - NLM STAT- MEDLINE DCOM- 20210930 LR - 20240216 IS - 1539-7262 (Electronic) IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 61 IP - 11 DP - 2020 Nov TI - Chylomicronemia from GPIHBP1 autoantibodies. PG - 1365-1376 LID - 10.1194/jlr.R120001116 [doi] AB - Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody-based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia. CI - Copyright (c) 2020 Miyashita et al. FAU - Miyashita, Kazuya AU - Miyashita K AD - Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. AD - Immuno-Biological Laboratories (IBL), Fujioka, Gunma, Japan. FAU - Lutz, Jens AU - Lutz J AD - Medical Clinic, Nephrology-Infectious Diseases, Central Rhine Hospital Group, Koblenz, Germany. FAU - Hudgins, Lisa C AU - Hudgins LC AD - Rogosin Institute, Weill Cornell Medical College, New York, NY, USA. FAU - Toib, Dana AU - Toib D AD - Department of Pediatrics, Drexel University, Philadelphia, PA, USA. AD - Section of Pediatric Rheumatology, St. Christopher's Hospital for Children, Philadelphia, PA, USA. FAU - Ashraf, Ambika P AU - Ashraf AP AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Song, Wenxin AU - Song W AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. FAU - Murakami, Masami AU - Murakami M AD - Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. FAU - Nakajima, Katsuyuki AU - Nakajima K AD - Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. FAU - Ploug, Michael AU - Ploug M AUID- ORCID: 0000-0003-2215-4265 AD - Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. AD - Biotechnology Research Innovation Center, Copenhagen University, Copenhagen, Denmark. FAU - Fong, Loren G AU - Fong LG AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA abeigneux@mednet.ucla.edu lfong@mednet.ucla.edu sgyoung@mednet.ucla.edu. FAU - Young, Stephen G AU - Young SG AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA abeigneux@mednet.ucla.edu lfong@mednet.ucla.edu sgyoung@mednet.ucla.edu. AD - Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. FAU - Beigneux, Anne P AU - Beigneux AP AUID- ORCID: 0000-0002-7892-150X AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA abeigneux@mednet.ucla.edu lfong@mednet.ucla.edu sgyoung@mednet.ucla.edu. LA - eng GR - P01 HL090553/HL/NHLBI NIH HHS/United States GR - R01 HL087228/HL/NHLBI NIH HHS/United States GR - R01 HL125335/HL/NHLBI NIH HHS/United States GR - R35 HL139725/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200918 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Autoantibodies) RN - 0 (GPIHBP1 protein, human) RN - 0 (Receptors, Lipoprotein) SB - IM MH - Autoantibodies/*immunology MH - Humans MH - Hypertriglyceridemia/*immunology MH - Receptors, Lipoprotein/*immunology PMC - PMC7604722 OTO - NOTNLM OT - autoimmune disease OT - glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 OT - immunoglobulin A OT - immunoglobulin G4 OT - lipoprotein lipase OT - triglycerides COIS- Conflict of interest-K,N. holds stock in Immuno-Biological Laboratories (IBL) and serves as a consultant for Skylight and Sysmex. All other authors declare that they have no conflicts of interest with the contents of this article. EDAT- 2020/09/20 06:00 MHDA- 2021/10/01 06:00 PMCR- 2021/11/01 CRDT- 2020/09/19 05:29 PHST- 2020/09/20 06:00 [pubmed] PHST- 2021/10/01 06:00 [medline] PHST- 2020/09/19 05:29 [entrez] PHST- 2021/11/01 00:00 [pmc-release] AID - S0022-2275(20)43725-3 [pii] AID - r120001116 [pii] AID - 10.1194/jlr.R120001116 [doi] PST - ppublish SO - J Lipid Res. 2020 Nov;61(11):1365-1376. doi: 10.1194/jlr.R120001116. Epub 2020 Sep 18.