Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis
Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis
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DOI：
10.1016/j.kint.2016.04.003
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发表时间：
2016-09-01
影响因子：
19.6
通讯作者：
Sethi, Sanjeev
中科院分区：
文献类型：
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作者：
Dasari, Surendra;Amin, Md. Shahrier;Sethi, Sanjeev
载脂蛋白A-IV相关性淀粉样变性（AApoAIV淀粉样变性）是一种罕见的原因淀粉样变性，只有一个单一的报告病例。在这里，我们描述了11例肾AApoAIV淀粉样变性病例的临床、活检和质谱特征，包括9例男性和2例女性，诊断时平均年龄为63.5岁。进行性慢性肾脏疾病（平均血清肌酐2.9 mg/dl）是活检的最常见原因，除1例外，所有患者均无蛋白尿或蛋白尿极轻微。9例患者的血液学和血清学评价为阴性，而2例患者有单克隆丙种球蛋白病。肾活检结果显著，显示大量嗜酸性刚果红阳性淀粉样沉积物局限于肾髓质，肾皮质除外。在6例病例中，除间质受累外，还观察到肾小管周围淀粉样蛋白。免疫荧光研究对免疫球蛋白呈阴性。电子显微镜显示直径为7至10纳米的无分支原纤维。激光显微切割淀粉样蛋白沉积物，然后进行质谱分析，结果显示AApoAIV蛋白的光谱数（半定量丰度测量）范围为49至169（平均85），血清淀粉样蛋白（平均19）和载脂蛋白E（平均48）。重要的是，没有检测到任何其他形式的已知淀粉样前体蛋白的肽。因此，肾AApoAIV淀粉样变性通常表现为进行性慢性肾病，并且在组织学上表现出广泛的髓质受累，皮质保留。最好通过质谱法进行诊断。因此，需要高度怀疑并检查肾髓质才能作出诊断。
Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis.