An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the GPIHBP1 autoantibody syndrome

Miyashita, Kazuya; Fukamachi, Isamu; Machida, Tetsuo; Nakajima, Kiyomi; Young, Stephen G.; Murakami, Masami; Beigneux, Anne P.; Nakajima, Katsuyuki

doi:10.1016/j.cca.2018.09.039

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…Chylomicronemia occasionally appears spontaneously, and some of these ''acquired'' cases are caused by GPIHBP1 autoantibodies (''GPIHBP1 autoantibody syndrome'') (Beigneux et al, 2017;Eguchi et al, 2019;Hu et al, 2017a;Kersten, 2017). This disorder was discovered fortuitously while characterizing a monoclonal antibody-based ELISA designed to measure plasma levels of GPIHBP1 (Beigneux et al, 2017;Miyashita et al, 2018a). In those studies, two plasma samples, both from patients with chylomicronemia, had abnormally low GPIHBP1 levels, and the GPIHBP1 levels remained low even after ''spiking'' the plasma samples with recombinant GPIHBP1.…”

Section: Chylomicronemia From Gpihbp1 Autoantibodiesmentioning

confidence: 99%

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GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism

et al. 2019

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Section: Chylomicronemia From Gpihbp1 Autoantibodiesmentioning

confidence: 99%

“…It will also be important to determine if immune complexes are present in the plasma of affected patients. The presence of immune complexes could have been overlooked by the ELISAs used to detect GPIHBP1 autoantibodies (Beigneux et al, 2017;Miyashita et al, 2018a).…”

Section: Chylomicronemia From Gpihbp1 Autoantibodiesmentioning

confidence: 99%

GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism

et al. 2019

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“…A diagnosis of the GPIHBP1 antibody syndrome in patients with hypertriglyceridemia fundamentally depends on documenting GPIHBP1 autoantibodies in serum or plasma. GPIHBP1 autoantibodies can be identified quite easily with an ELISA (35,82). Dilutions of serum or plasma are incubated on 96-well plates coated with recombinant GPIHBP1.…”

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confidence: 99%

Chylomicronemia from GPIHBP1 autoantibodies

Miyashita

Lutz²,

Hudgins

et al. 2020

Journal of Lipid Research

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Some cases of chylomicronemia are caused by autoantibodies against GPIHBP1, an endothelial cell protein that shuttles lipoprotein lipase (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 5 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.

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“…After obtaining the informed consent, targeted exon sequencing was performed to investigate 36 lipid-related genes (LDLR, PCSK9, ApoB, LDLRAP1, ABCG5, ABCG8, LCAT, ABCA1, LPL, ApoC-II, ApoC-III, ApoA-V, GPIHBP1, LMF1, which was first reported by Kihara et al in 1989 3) . Recently, a monoclonal antibody against human GPIHBP1 in plasma was developed by Miyashita et al 4) , and autoimmune hyperchylomicronemia with anti-GPIHBP1 antibodies was reported by Beigneux AP et al in 2017 5) . GPIHBP1 is a glycolipid-modified anchor protein that resides on capillary endothelial cell membranes and plays a role in transporting LPL from outside the capillaries into the lumen of blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Anti-GPIHBP1 Antibody-Positive Autoimmune Hyperchylomicronemia and Immune Thrombocytopenia

Tanaka

Koseki

Kato

et al. 2023

JAT

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Primary hyperchylomicronemia is characterized by marked hypertriglyceridemia exceeding 1,000 mg/dL. It is caused by dysfunctional mutations in specific genes, namely those for lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), apolipoprotein C2 (ApoC-II), lipase maturation factor 1 (LMF1), or apolipoprotein A5 (ApoA-V). Importantly, antibodies against LPL or GPIHBP1 have also been reported to induce autoimmune hyperchylomicronemia.The patient was a 46-year-old man diagnosed with immune thrombocytopenia (ITP) at 41 years. At the time, he was administered prednisolone (PSL) and eltrombopag, a thrombopoietin receptor agonist. At 44 years, he suffered from acute myocardial infarction, and PSL was discontinued to avoid enhancing atherogenic risks. He was maintained on eltrombopag monotherapy. After discontinuing PSL, marked hypertriglyceridemia (＞3,000 mg/dL) was observed, which did not improve even after a few years of pemafibrate therapy. Upon referral to our clinic, the triglyceride (TG) level was 2,251 mg/dL, ApoC-II was 19.8 mg/dL, LPL was 11.1 ng/mL (0.02-1.5 ng/mL), GPIHBP1 was 47.7 pg/mL (740.0-1,014.0 pg/mL), and anti-GPIHBP1 antibody was detected. The patient was diagnosed to have anti-GPIHBP1 antibody-positive autoimmune hyperchylomicronemia. He was administered PSL 15 mg/day, and TG levels were controlled at approximately 200 mg/dL.Recent studies have reported that patients with anti-GPIHBP1 antibody-induced autoimmune hyperchylomicronemia had concomitant rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's disease, and Graves' disease. We report a rare case of anti-GPIHBP1 antibody-positive autoimmune hyperchylomicronemia with concomitant ITP, which became apparent when PSL was discontinued due to the onset of steroid-induced acute myocardial infarction.

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An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the GPIHBP1 autoantibody syndrome

Cited by 9 publications

References 17 publications

GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism

GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism

Chylomicronemia from GPIHBP1 autoantibodies

Anti-GPIHBP1 Antibody-Positive Autoimmune Hyperchylomicronemia and Immune Thrombocytopenia

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