Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin.
Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin.
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DOI：
10.1038/s41598-017-01775-4
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发表时间：
2017-05-08
影响因子：
4.6
通讯作者：
Ando Y
中科院分区：
文献类型：
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作者：
Suenaga G;Ikeda T;Masuda T;Motokawa H;Yamashita T;Takamatsu K;Misumi Y;Ueda M;Matsui H;Senju S;Ando Y
家族性淀粉样多发性神经病（FAP），这是由突变的甲状腺素运载蛋白（TTR），和炎症之间的关系只是最近才注意到。为了确定FAP携带者和患者中是否存在炎症，检测了57名健康供体（HD）、21名FAP携带者和66名FAP患者的血清白细胞介素（IL）-6浓度，并通过多元回归分析和结构方程模型（SEM）评估了各组中IL-6与TTR之间的关系。与HD相比，FAP携带者（p = 0.001，95% CI 0.398-1.571）和患者（p = 0.002，95% CI 0.362-1.521）中IL-6浓度升高。此外，SEM表明FAP携带者中IL-6和TTR之间呈正相关（p = 0.010，95%CI 0.019-0.140），但在HD和FAP患者中则不存在。此外，我们确定TTR是否诱导促炎细胞因子的离体产生。与野生型TTR相比，来自HD和FAP患者的HD衍生的CD 14+单核细胞和诱导多能干细胞衍生的髓系细胞在突变和聚集的TTR条件下剂量依赖性地产生IL-6。总之，FAP携带者和患者处于炎症状态，突变的TTR的存在是炎症的触发因素，特别是在FAP携带者中。
The relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)−6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0.001, 95% CI 0.398–1.571) and patients (p = 0.002, 95% CI 0.362–1.521). Further, SEM indicated a positive relationship between IL-6 and TTR in FAP carriers (p = 0.010, 95% CI 0.019–0.140), but not in HD and FAP patients. In addition, we determined whether TTR induces production of pro-inflammatory cytokines ex vivo. HD-derived CD14 + monocytes and induced pluripotent stem cell-derived myeloid lineage cells from a HD and FAP patient dose-dependently produced IL-6 under mutated and aggregated TTR conditions, compared with wild-type TTR. In conclusion, FAP carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers.