BACKGROUND The commonly used methods for amyloid typing include immunofluorescence or immunohistochemistry (IHC), which sometimes may come with diagnostic pitfalls. Mass spectrometry (MS)-based proteomics has been recognized as a reliable technique in amyloid typing. CASE PRESENTATION We reported two middle-aged patients who presented with proteinuria, hypertension and normal renal function, and both had a family history of renal diseases. The renal biopsies of both patients revealed renal amyloidosis with the similar pattern by massive exclusively glomerular amyloid deposition. The IHC was performed by using a panel of antibodies against the common types of systemic amyloidosis, and demonstrated co-deposition of fibrinogen Aα chain and apolipoprotein A-I in the glomerular amyloid deposits of each patient. Then the MS on amyloid deposits captured by laser microdissection (LMD/MS) and genetic study of gene mutations were investigated. The large spectra corresponding to ApoA-I in case 1, and fibrinogen Aα chain in case 2 were identified by LMD/MS respectively. Further analysis of genomic DNA mutations demonstrated a heterozygous mutation of p. Trp74Arg in ApoA-I in case 1, and a heterozygous mutation of p. Arg547GlyfsTer21 in fibrinogen Aα chain in case 2. CONCLUSIONS The current study revealed that IHC was not reliable for accurate amyloid typing, and that MS-based proteomics and genetic analysis were essential for typing of hereditary amyloidosis.

中文翻译：

---

遗传性肾淀粉样变性的分型，表现为孤立性肾小球淀粉样蛋白沉积。

背景技术淀粉样蛋白分型的常用方法包括免疫荧光或免疫组织化学（IHC），有时可能伴随诊断缺陷。基于质谱（MS）的蛋白质组学已被认为是淀粉样蛋白分型的可靠技术。病例介绍我们报告了两名中蛋白蛋白尿，高血压和正常肾功能的中年患者，均具有肾脏疾病家族病史。两名患者的肾脏活检均显示肾淀粉样变性病具有类似的模式，仅是大量肾小球淀粉样蛋白沉积。通过使用针对常见类型的系统性淀粉样变性的一组抗体进行IHC，并证明了每位患者肾小球淀粉样蛋白沉积物中纤维蛋白原Aα链和载脂蛋白AI的共沉积。然后研究了通过激光显微切割（LMD / MS）捕获的淀粉样蛋白沉积物的质谱，并对基因突变进行了遗传研究。分别通过LMD / MS鉴定出与案例1中的ApoA-I和案例2中的纤维蛋白原Aα链相对应的大光谱。基因组DNA突变的进一步分析表明p的杂合突变。案例1中ApoA-I中的Trp74Arg和p的杂合突变。案例2中纤维蛋白原Aα链中的Arg547GlyfsTer21。结论本研究表明，IHC对于准确的淀粉样蛋白分型并不可靠，基于MS的蛋白质组学和遗传分析对于遗传性淀粉样变性病的分型至关重要。用LMD / MS分别鉴定病例2中的Aβ和纤维蛋白原Aα链。基因组DNA突变的进一步分析表明p的杂合突变。案例1中ApoA-I中的Trp74Arg和p的杂合突变。案例2中纤维蛋白原Aα链中的Arg547GlyfsTer21。结论本研究表明，IHC对于准确的淀粉样蛋白分型并不可靠，基于MS的蛋白质组学和遗传分析对于遗传性淀粉样变性病的分型至关重要。用LMD / MS分别鉴定病例2中的Aβ和纤维蛋白原Aα链。基因组DNA突变的进一步分析表明p的杂合突变。案例1中ApoA-I中的Trp74Arg和p的杂合突变。案例2中纤维蛋白原Aα链中的Arg547GlyfsTer21。结论本研究表明，IHC对于准确的淀粉样蛋白分型并不可靠，基于MS的蛋白质组学和遗传分析对于遗传性淀粉样变性病的分型至关重要。