Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
Department of Hematology and Oncology, Osaka University Graduate School of Medicine.
J Atheroscler Thromb. 2023 Jan 1;30(1):100-104. doi: 10.5551/jat.63348. Epub 2022 Feb 18.
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.
原发性高乳糜微粒血症的特征是甘油三酯显著升高,超过 1000mg/dL。它是由特定基因的功能障碍突变引起的,即脂蛋白脂肪酶(LPL)、糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1(GPIHBP1)、载脂蛋白 C2(ApoC-II)、脂肪酶成熟因子 1(LMF1)或载脂蛋白 A5(ApoA-V)的基因突变。重要的是,针对 LPL 或 GPIHBP1 的抗体也被报道可诱导自身免疫性高乳糜微粒血症。患者为 46 岁男性,41 岁时被诊断为免疫性血小板减少症(ITP)。当时给予泼尼松龙(PSL)和促血小板生成素受体激动剂艾曲泊帕治疗。44 岁时,他发生急性心肌梗死,停用 PSL 以避免增强动脉粥样硬化风险。他接受艾曲泊帕单药治疗。停用 PSL 后,出现明显的高甘油三酯血症(>3000mg/dL),即使经过几年的 pemafibrate 治疗也没有改善。转至我院就诊时,患者的甘油三酯(TG)水平为 2251mg/dL,载脂蛋白 C-II 为 19.8mg/dL,脂蛋白脂肪酶为 11.1ng/mL(0.02-1.5ng/mL),GPIHBP1 为 47.7pg/mL(740.0-1014.0pg/mL),并检测到抗 GPIHBP1 抗体。该患者被诊断为抗 GPIHBP1 抗体阳性的自身免疫性高乳糜微粒血症。给予泼尼松龙 15mg/d 治疗,TG 水平控制在 200mg/dL 左右。最近的研究报道称,抗 GPIHBP1 抗体诱导的自身免疫性高乳糜微粒血症患者同时患有类风湿关节炎、系统性红斑狼疮、干燥综合征、桥本甲状腺炎和格雷夫斯病。我们报告了一例罕见的抗 GPIHBP1 抗体阳性的自身免疫性高乳糜微粒血症合并 ITP 的病例,由于类固醇诱导的急性心肌梗死,停用 PSL 后,这种疾病变得明显。