摘要
在許多種類的類澱粉神經病變 (amyloid neuropathy) 中，transthyretin (TTR) mutation已知是導致家族性類澱粉多發性神經病變 (Familial amyloid polyneuropathy, FAP) 的主要原因，其中最常見的是Val30Met，而在台灣的是Ala97Ser。FAP患者通常會在不自覺的情況下發現腳出現感覺麻木 (numbness) 和輕度癱瘓 (weakness) 的現象，可能還伴隨著腸胃不適的症狀，因此有些病人會到腸胃科去看診但是卻找不出原因。 台灣的案例在過去的研究已經發現，FAP患者的腓腸神經 (sural nerve) 組織切片上，利用組織化學染色可發現血管的周圍會有eosinophilic現象以及容易有Congo red濃染的現象，利用TTR抗體進行免疫組織化學染色，可以在相同的位置觀察到免疫染色現象。而在葡萄牙亦有學者發現FAP患者的腓腸神經的神經內膜 (endoneurium) 裡有cytokines增加的情形，血管內皮細胞株若額外給予fibrillar TTR，亦可使細胞產生cytokines。但是至今對於如何導致神經退化的機制仍然不清楚。 根據前人的發現，本實驗假設FAP的腓腸神經內應該會有免疫細胞的浸潤現象，而血管可能會有發炎現象，若能發現免疫細胞浸潤現象，則希望能進一步探討此現象與神經退化程度是否有關，以及FAP病人的有髓鞘神經纖維與無髓鞘神經纖維的退化程度是否有所差異。 從型態學觀察後發現，FAP腓腸神經內的有髓鞘神經纖維密度與表皮神經纖維密度有顯著正相關，顯示兩者的退化程度是相似的。經過免疫組織化學染色後，發現在FAP的腓腸神經內巨噬細胞及T細胞均有顯著的浸潤現象，而T細胞與神經退化程度均無呈現相關性，但是巨噬細胞與有髓鞘神經纖維呈現顯著正相關。在血管的周圍則是發現部分FAP腓腸神經內的血管有補體反應現象。 本實驗發現Ala97Ser FAP的腓腸神經有T細胞浸潤以及補體反應，顯示這可能是發炎性神經病變，且可能與血管有關，但是TTR堆積是否真的跟發炎有關，進而導致神經退化，則需要更進一步連結TTR堆積、補體反應、免疫細胞浸潤與神經退化程度之間的關係才能更有說服力。
並列摘要
Familial amyloid polyneuropathy (FAP) due to mutations of transthyretin (TTR) contitutes important etiologies of amyloid neuropathy. In Portugal, Sweden, and Japan, the major mutation is Val30Met. In Taiwan, most FAP patients had Ala97Ser mutation. Neurological symptoms include numbness, weakness, dysautonomia, and diarrhoea. Previous studies have documented increased cytokines in endoneurium of sural nerve biopsy. These studies raise several issues, for example, what are the sources of cytokines. This study tested the hypothesis that whether the infiltration of immune cells was increased in sural nerve of FAP, and whether there is correlation between immune cell infiltration and nerve degeneration. The myelinated fiber density of sural nerve was proportional to intraepidermal nerve fiber (IENF) density on skin biopsies. The infiltrations of macrophages and T cells in sural nerves of FAP was increased compared to that of control subjects. There was complement-deposition in blood vessels of some in FAP patients. Keywords: Familial amyloid polyneuropathy (FAP), Ala97Ser, axonal degeneration, macrophage, T cell.
參考文獻
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