Departments of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
J Am Soc Nephrol. 2013 Jul;24(8):1305-12. doi: 10.1681/ASN.2012090913. Epub 2013 Apr 25.
Lecithin-cholesterol acyltransferase (LCAT) is an enzyme involved in maintaining cholesterol homeostasis. In familial LCAT deficiency (FLD), abnormal lipid deposition causes renal injury and nephrotic syndrome, frequently progressing to ESRD. Here, we describe a 63-year-old Japanese woman with no family history of renal disease who presented with nephrotic syndrome. The laboratory data revealed an extremely low level of serum HDL and undetectable serum LCAT activity. Renal biopsy showed glomerular lipid deposition with prominent accumulation of foam cells, similar to the histologic findings of FLD. In addition, she had subepithelial electron-dense deposits compatible with membranous nephropathy, which are not typical of FLD. A mixing test and coimmunoprecipitation study demonstrated the presence of an inhibitory anti-LCAT antibody in the patient's serum. Immunohistochemistry and immunofluorescence detected LCAT along parts of the glomerular capillary walls, suggesting that LCAT was an antigen responsible for the membranous nephropathy. Treatment with steroids resulted in complete remission of the nephrotic syndrome, normalization of serum LCAT activity and HDL level, and disappearance of foam cell accumulation in renal tissue. In summary, inhibitory anti-LCAT antibody can lead to glomerular lesions similar to those observed in FLD.
卵磷脂胆固醇酰基转移酶（LCAT）是参与维持胆固醇稳态的一种酶。在家族性 LCAT 缺乏症（FLD）中，异常的脂质沉积会导致肾脏损伤和肾病综合征，常进展为终末期肾病。在这里，我们描述了一位 63 岁的日本女性，她没有肾脏疾病的家族史，表现为肾病综合征。实验室数据显示血清高密度脂蛋白极低，血清 LCAT 活性无法检测到。肾脏活检显示肾小球脂质沉积，有明显的泡沫细胞积聚，类似于 FLD 的组织学发现。此外，她还伴有符合膜性肾病的上皮下电子致密沉积物，这与 FLD 不典型。混合试验和共沉淀研究表明，患者血清中存在抑制性抗 LCAT 抗体。免疫组织化学和免疫荧光检测到 LCAT 存在于部分肾小球毛细血管壁上，表明 LCAT 是导致膜性肾病的抗原。皮质类固醇治疗导致肾病综合征完全缓解，血清 LCAT 活性和 HDL 水平正常化，肾脏组织中泡沫细胞积聚消失。综上所述，抑制性抗 LCAT 抗体可导致类似于 FLD 观察到的肾小球病变。
