Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation
Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation
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DOI：
10.1136/jnnp-2013-305973
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发表时间：
2014-07-01
影响因子：
11
通讯作者：
Ando, Yukio
中科院分区：
文献类型：
--
作者：
Oshima, Toshinori;Kawahara, Satomi;Ando, Yukio
目的探讨肝移植（LT）对家族性淀粉样多发性神经病（FAP）的远期影响。方法对4例肝移植后存活10年以上的FAP患者和7例无肝移植的FAP患者进行尸检，观察其临床病理和全身组织生化特征。结果心脏、舌、脊髓等组织中有中度至重度淀粉样蛋白沉积，其他组织无或轻度淀粉样蛋白沉积。这些发现似乎与老年系统性淀粉样变性（SSA）中观察到的结果相似，SSA是一种由野生型（WT）TTR引起的散发性淀粉样变性。此外，在LT后的患者中，除脊髓外的全身组织部位中的淀粉样蛋白沉积主要来自正常肝移植物分泌的WT TTR。此外，在非移植患者中，WT TTR的比例似乎在LT后患者具有严重淀粉样蛋白沉积的那些组织部位中相对较高，这表明WT TTR倾向于在那些组织部位中形成淀粉样蛋白。最后，虽然淀粉样沉积物中TTR的截短并不依赖于接受LT，但我们阐明了TTR的截短主要发生在日本非流行区的患者中，与日本流行区的患者相比，FAP淀粉样TTR V30 M患者发病较晚，发病率较低。这似乎与SSA的过程相似。淀粉样沉积物中TTR的截短可能取决于一些遗传或环境因素，而不是LT。
Objective To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP).Methods We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients.Results Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan.Conclusions FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.