Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
J Nephrol. 2018 Jun;31(3):343-350. doi: 10.1007/s40620-017-0426-6. Epub 2017 Aug 21.
Renal amyloidosis is characterized by acellular Congo red positive deposits in the glomeruli, interstitium and/or arteries. Light chain restriction on immunofluorescence studies is present in AL-amyloidosis, the most common type of amyloidosis involving the kidney. The detection of Congo red positive deposits coupled with negative immunofluorescence studies is highly suggestive of non-AL amyloidosis. Some of the non-AL amyloidosis are common while others are relatively rare. The clinical features, laboratory and renal pathology findings are helpful in the diagnosis and typing of non-AL amyloidosis. Thus, ALECT2 amyloidosis is characterized by diffuse cortical interstitial amyloid deposits, AA amyloidosis shows vascular deposits in addition to the glomerular deposits, AFib amyloidosis is characterized by massive amyloid accumulation limited to the glomeruli resulting in the obliteration of glomerular architecture, AApoA1 and AApoAIV are characterized by large amyloid deposits restricted to the medulla, and AGel shows swirling patterns of amyloid fibrils on electron microscopy. While light microscopy is very helpful, accurate typing of non-AL amyloidosis then requires immunohistochemical or laser microdissection/mass spectrometry studies of the Congo red positive deposits. Immunohistochemical studies are available for some of the non-AL amyloidosis. On the other hand, mass spectrometry analysis is a one stop methodology for confirmation and typing of amyloidosis. The diagnosis and typing of amyloidosis by mass spectrometry is based on finding the signature amyloid peptides, apolipoprotein E and serum amyloid-P component, followed by detection of precursor amyloidogenic protein such as LECT2, fibrinogen-α, gelsolin, etc. To, summarize, non-AL amyloidosis is a group of amyloidosis with distinctive clinical, laboratory and renal pathology findings. Typing of the amyloidosis is best performed using mass spectrometry methodology. Accurate typing of non-AL amyloidosis is imperative for correct management, prognosis, and genetic counseling.
肾脏淀粉样变性的特征是肾小球、间质和/或动脉中无细胞刚果红阳性沉积物。免疫荧光研究中存在轻链限制，这是肾脏最常见的淀粉样变性类型。刚果红阳性沉积物的检测加上免疫荧光研究阴性高度提示非 AL 淀粉样变性。一些非 AL 淀粉样变性很常见，而另一些则相对罕见。临床特征、实验室和肾脏病理发现有助于非 AL 淀粉样变性的诊断和分型。因此，ALECT2 淀粉样变性的特征是弥漫性皮质间质淀粉样沉积物，AA 淀粉样变性除了肾小球沉积物外还显示血管沉积物，AFib 淀粉样变性的特征是大量淀粉样物质局限于肾小球，导致肾小球结构消失，AApoA1 和 AApoAIV 的特征是大的淀粉样物质局限于髓质，AGel 在电子显微镜下显示出淀粉样纤维的漩涡状图案。虽然光镜非常有帮助，但非 AL 淀粉样变性的准确分型还需要刚果红阳性沉积物的免疫组化或激光微切割/质谱研究。一些非 AL 淀粉样变性有免疫组化研究。另一方面，质谱分析是一种用于确认和分型淀粉样变性的一站式方法。通过质谱分析诊断和分型淀粉样变性是基于发现特征性淀粉样肽、载脂蛋白 E 和血清淀粉样蛋白 P 成分，然后检测前体淀粉样原蛋白，如 LECT2、纤维蛋白原-α、凝胶蛋白等。总之，非 AL 淀粉样变性是一组具有独特临床、实验室和肾脏病理表现的淀粉样变性。淀粉样变性的分型最好使用质谱方法学进行。非 AL 淀粉样变性的准确分型对于正确的管理、预后和遗传咨询至关重要。
