ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger

Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.
205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.
Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.
Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.

针对扳机指（trigger finger）手术治疗中获取的组织标本进行组织学检查时，我们常在环状韧带中发现无法分类的淀粉样沉积物。本研究通过组织学、免疫组织化学（immunohistochemistry）以及基于定量质谱的蛋白质组学开展综合分析，对这类未知类型的淀粉样物质进行了系统探究。
本研究从172例患者体内获取了205份环状韧带组织标本。所有标本均接受组织学与免疫组织化学检测。其中，经组织学证实存在环状韧带淀粉样变的10例患者的组织标本，采用无标记定量蛋白质组学（label-free quantitative proteomics）进行分析。研究同时将组织学与免疫组织化学结果与患者人口统计学特征进行关联分析。
淀粉样物质可表现为沿环状韧带表面分布的带状沉积物，以及基质内的点状或斑片状沉积物。免疫组织化学检测在92份标本中检出转甲状腺素蛋白淀粉样变（ATTR amyloid），此类沉积物多呈基质内斑片状；而100份标本的带状沉积物仍无法分类。蛋白质组学谱分析显示，该未知淀粉样物质极有可能来源于纤维蛋白原。研究团队随后使用定制抗体对全部队列标本进行了免疫组织化学复检，证实环状韧带中此前无法分类的淀粉样沉积物内存在纤维蛋白原α链（FGA）。
本研究证实，环状韧带受累的淀粉样变存在两种不同类型：转甲状腺素蛋白淀粉样变（ATTR amyloid）与纤维蛋白原相关性淀粉样变（AFib amyloid），二者具有截然不同的患者人口统计学特征与组织形态学沉积模式。