Feingold K R, Castro G R, Ishikawa Y, Fielding P E, Fielding C J
Medical Service, Veterans Administration Medical Center, San Francisco, California 94121.
J Clin Invest. 1989 Mar;83(3):796-802. doi: 10.1172/JCI113960.
In the present report we describe a patient with multiple myeloma and long-standing paraproteinemia who developed xanthoma in the absence of an elevation in plasma cholesterol or triglyceride concentrations. Studies demonstrated that our patient's monoclonal IgG antibody interacted with apoprotein B-100. The LDL-antibody complex isolated from our patient did not affect the degradation of LDL by human fibroblasts, indicating that while IgG derived from our patient interacted with LDL it did not alter the metabolism of this lipoprotein by the LDL receptor pathway. Since the LDL receptor pathway is the major route of LDL metabolism, this probably explains why our patient was not hyperlipidemic. In contrast to an absence of effect on the LDL receptor, our patient's LDL-antibody complex stimulated cholesterol esterification within macrophages indicating the uptake and degradation of the LDL-antibody complex. The LDL-antibody complex inhibited the degradation of acetyl LDL by macrophages (scavenger pathway), demonstrating that our patient's LDL-antibody complex was recognized as a modified LDL. Moreover, mixing Ig from our patient with normal LDL also resulted in the normal LDL increasing the esterification of cholesterol by macrophages. One can hypothesize that our patient's monoclonal IgG-LDL complex interacted with the macrophage scavenger receptor, thereby resulting in the occurrence of xanthoma in the absence of hyperlipidemia.
在本报告中,我们描述了一名患有多发性骨髓瘤和长期副蛋白血症的患者,该患者在血浆胆固醇或甘油三酯浓度未升高的情况下出现了黄瘤。研究表明,我们患者的单克隆IgG抗体与载脂蛋白B - 100相互作用。从我们患者分离出的LDL - 抗体复合物并不影响人成纤维细胞对LDL的降解,这表明虽然我们患者的IgG与LDL相互作用,但它并未通过LDL受体途径改变这种脂蛋白的代谢。由于LDL受体途径是LDL代谢的主要途径,这可能解释了为什么我们的患者没有高脂血症。与对LDL受体没有影响相反,我们患者的LDL - 抗体复合物刺激了巨噬细胞内的胆固醇酯化,表明LDL - 抗体复合物被摄取和降解。LDL - 抗体复合物抑制了巨噬细胞对乙酰LDL的降解(清道夫途径),证明我们患者的LDL - 抗体复合物被识别为修饰的LDL。此外,将我们患者的Ig与正常LDL混合也导致正常LDL增加了巨噬细胞对胆固醇的酯化。可以推测,我们患者的单克隆IgG - LDL复合物与巨噬细胞清道夫受体相互作用,从而在无高脂血症的情况下导致了黄瘤的发生。