Evidence of Concurrent Light Chain and Transthyretin Cardiac Amyloidosis in 2 Patients.
Evidence of Concurrent Light Chain and Transthyretin Cardiac Amyloidosis in 2 Patients.
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DOI：
10.1016/j.jaccao.2020.01.001
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发表时间：
2020-03
期刊：
影响因子：
--
通讯作者：
Hanna M
中科院分区：
文献类型：
--
作者：
Donnelly JP;Gabrovsek A;Sul L;Cotta C;Rodriguez ER;Tan CD;Hanna M
两种不同类型的系统性淀粉样变性：轻链 (AL) 和运甲状腺素蛋白 (ATTR)，占诊断的心脏淀粉样变性 (CA) 的 95% 以上(1)。 AL 源自浆细胞克隆群，这些浆细胞产生错误折叠的免疫球蛋白轻链，并在心脏、肾脏、外周神经和自主神经、肝脏和胃肠道等器官中聚集 (1)。 ATTR 源自肝脏来源的运甲状腺素蛋白 (TTR)，该蛋白变得动力学不稳定、错误折叠并聚集成淀粉样原纤维。这种情况可能是由于遗传性点突变（ATTRv 表示“变体”）而发生，或者是作为一种称为野生型 (ATTRwt)(1) 的形式获得的，这种突变最常与衰老相关。 ATTRv 影响外周神经、自主神经和/或心脏，表型因突变而异，而 ATTRwt 则表现出以心脏为主的表型 (1)。用于诊断淀粉样变性的传统方法是使用刚果红或硫黄素 S 染色对受影响的器官进行组织学确认 (2)。使用免疫组织化学 (IHC) 或液相色谱串联质谱 (LC-MS/MS) (2) 对淀粉样原纤维蛋白含量进行进一步表征。确定淀粉样变性的类型至关重要，因为 AL 和 ATTR 淀粉样变性的预后和治疗显着不同 (1)。目前的分析技术非常擅长区分这两种类型；然而，有时，通过识别淀粉样蛋白沉积物中是否存在多种前体蛋白，包括 AL 和 TTR 共沉积的报告，可能会造成诊断混乱 (3-5)。在此，我们介绍了 2 例具有 ATTR 和 AL-CA 同时发生的临床和组织学证据的病例。
Two distinct types of systemic amyloidosis, light chain (AL) and transthyretin (ATTR), account for> 95% of diagnosed cardiac amyloidosis (CA)(1). AL arises from a clonal population of plasma cells that produce misfolded immunoglobulin light chains that aggregate in organs such as the heart, kidneys, peripheral and autonomic nerves, liver, and gastrointestinal tract (1). ATTR arises from the liver-derived protein transthyretin (TTR) that becomes kinetically unstable, misfolds, and aggregates into amyloid fibrils. This can occur due to a hereditary point mutation (ATTRv for “variant”) or is acquired as a form known as wild-type (ATTRwt)(1), which is most commonly associated with aging. ATTRv affects the peripheral and autonomic nerves and/or the heart, with the phenotype varying depending on the mutation, whereas ATTRwt exhibits a more cardiac-dominant phenotype (1).The traditional method used to diagnose amyloidosis is histological confirmation of the affected organ using Congo red or thioflavin S staining (2). Further characterization of the amyloid fibril protein content is made using immunohistochemistry (IHC) or liquid chromatography tandem mass spectrometry (LC-MS/MS)(2). Determination of the type of amyloidosis is crucial because the prognosis and treatment significantly differ between AL and ATTR amyloidosis (1). Current analytical techniques are very good at distinguishing the 2 types; however, occasionally, there can be diagnostic confusion by identifying the presence of multiple precursor proteins in an amyloid deposit, including reports of co-deposition of AL and TTR (3–5). Herein, we present 2 cases with clinical and histological evidence of both ATTR and AL-CA occurring concurrently.
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