Acquired Chylomicronemia Due to Autoantibodies Against GPIHBP1

Abstract

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis We report a case of recurrent triglyceride-induced pancreatitis that was found to be due to autoantibodies to glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1) in the setting of biopsy-proven membranous lupus nephritis. Objective/Purpose This case report highlights a very rare cause of acquired chylomicronemia and discusses the treatment of GPIHBP1 autoantibody-induced hypertriglyceridemia. Methods A 12-year-old female with no medical history was admitted to the hospital for triglyceride induced pancreatitis. Her initial lipids consisted of: triglycerides 4070, total cholesterol 290, HDLc 9, and non-HDL-c 281 mg/dL. After inpatient treatment, she was started on fenofibrate and referred to lipid clinic. Despite fenofibrate 160 mg daily, icosapent ethyl 2 g twice a day, and a strict low-fat diet, the patient continued to experience triglyceride-induced pancreatitis. Her triglycerides fluctuated between 1200 - 2300 mg/dL. Genotyping was negative for familial chylomicronemia (deficiency/mutation in LPL, APOC2, APOA5, LFM-1, and GPIHBP1). Therefore, the patient was presumed to have genotype-negative familial chylomicronemia syndrome. Over the next 2 years, the patient had 15 hospital admissions for triglyceride-induced pancreatitis. At age 14 she was started on alirocumab 75 mg injections every 14 days, which decreased, but did not eliminate, the frequency of pancreatitis episodes. Her triglyceride levels subsequently ranged 650 - 991 mg/dL. During a hospital admission at age 15, the patient was found to have nephrotic syndrome with an ANA titer >1:2560. Renal biopsy confirmed membranous lupus nephritis. She was treated with pulse-dose steroids, mycophenolate mofetil, and hydroxychloroquine. Her lupus diagnosis prompted testing for GPIHBP1 autoantibodies,which were strongly positive. Results Two months after our patient's diagnosis of GPIHBP1 autoantibody induced hypertriglyceridemia, she continues to receive treatment with prednisone 40 mg daily, mycophenolate mofetil 1000 mg twice a day, and hydroxychloroquine 200 mg daily and has received two doses of rituximab-pvvr 1000 mg. Her triglycerides remain elevated 1400 - 2200 mg/dL. Conclusions This case highlights a recently described entity in the literature, “GPIHBP1 autoantibody syndrome,” wherein patients with unexplained chylomicronemia are found to have autoantibodies to GPIHBP1, causing hypertriglyceridemia resistant to traditional medical therapy. Of the 33 known patients worldwide with GPIHBP1 autoantibody syndrome, immunosuppression with rituximab and mycophenolate are reported to be effective therapies.Our patient is currently undergoing immunosuppression, but triglyceride levels have yet to decrease. Additional time and/or rituximab doses may be needed in order to maximally suppress autoantibody production and, in turn, reduce triglyceride levels. Nothing to disclose.