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Abstract：
Hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy, also known as familial amyloid polyneuropathy (FAP), represents a progressive, heterogeneous, severe, and multisystemic disease caused by pathogenic variants in the TTR gene. This autosomal-dominant neurogenetic disorder has an adult onset with variable penetrance and an inconstant phenotype, even among subjects carrying the same mutation. Historically, ATTRv amyloidosis has been viewed as a non-inflammatory disease, mainly due to the absence of any mononuclear cell infiltration in ex vivo tissues; nevertheless, a role of inflammation in its pathogenesis has been recently highlighted. The immune response may be involved in the development and progression of the disease. Fibrillary TTR species bind to the receptor for advanced glycation end products (RAGE), probably activating the nuclear factor κB (NF-κB) pathway. Moreover, peripheral blood levels of several cytokines, including interferon (IFN)-gamma, IFN-alpha, IL-6, IL-7, and IL-33, are altered in the course of the disease. This review summarizes the current evidence supporting the role of the immune response in ATTRv amyloidosis, from the pathological mechanisms to the possible therapeutic implications.
摘要：
遗传性甲状腺素运载蛋白（ATTRv）淀粉样变性伴多发性神经病，也称为家族性淀粉样多发性神经病（FAP），代表一个进步，异质，严重,和由TTR基因的致病变异引起的多系统疾病。这种常染色体显性遗传的神经遗传病具有成人发作的外显率和不恒定的表型，甚至在携带相同突变的受试者中。历史上,ATTRv淀粉样变性被认为是一种非炎症性疾病，主要是由于离体组织中没有任何单核细胞浸润;然而，炎症在其发病机制中的作用最近被强调。免疫应答可能与疾病的发展和进展有关。纤维蛋白TTR物种与晚期糖基化终产物（RAGE）的受体结合，可能激活核因子κB（NF-κB）途径。此外，几种细胞因子的外周血水平，包括干扰素（IFN）-γ，IFN-α，IL-6、IL-7和IL-33在疾病过程中发生改变。这篇综述总结了目前支持免疫应答在ATTRv淀粉样变中的作用的证据。从病理机制到可能的治疗意义。
