Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine
Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine
复制标题
抗淀粉样变性甲状腺素运载蛋白 (ATTR) 抗体对家族性淀粉样变性多发性神经病 (FAP) 患者表型的影响 ATTR Valine30 蛋氨酸
DOI：
10.1016/j.cca.2013.02.002
复制
发表时间：
2013
期刊：
影响因子：
5
通讯作者：
Ando Y
中科院分区：
文献类型：
--
作者：
Obayashi K;Tasaki M;Jono H;Ueda M;Shinriki S;Misumi Y;Yamashita T;Oshima T;Nakamura T;Ikemizu S;Anan I;Suhr O;Ando Y
方法收集25例日本和6例瑞典FAP淀粉样蛋白原性甲状腺素运载蛋白（ATTR）缬氨酸30甲氨蝶呤（V30 M）患者、4例无症状的日本ATTR V30 M基因携带者和24例日本健康志愿者的血清标本。研究方法包括酶联免疫吸附试验（ELISA）和质谱法。结果3名日本和5名瑞典患者的ATTR抗体水平明显高于健康志愿者和无症状基因携带者（P<0.05）。抗体水平较高的8例患者均为晚发型病例。高抗体组血清中野生型TTR与ATTR V30 M的比例高于低抗体组。ELISA结果显示ATTR V30 M的24-35位和105-115位有两个表位。FAP患者24-35位抗体水平与发病年龄呈显著正相关（r=0.751，P<0.05）。在24- 35位抗原表位的患者中，抗体的出现率随年龄的增加而增加。结论这些发现有助于解释早发性和迟发性FAP的差异和/或FAP的进展。
BACKGROUNDThis study investigated whether a relationship exists between the presence of de novo antibodies and the clinical manifestations of familial amyloidotic polyneuropathy (FAP).METHODSSerum samples were collected from 25 Japanese and 6 Swedish FAP amyloidogenic transthyretin (ATTR) Valine30Methionine (V30M) patients, 4 asymptomatic Japanese ATTR V30M gene carriers, and 24 Japanese healthy volunteers. Study methods included enzyme-linked immunosorbent assay (ELISA) and mass spectrometry.RESULTSThree Japanese and 5 Swedish patients had significantly higher levels of antibodies against ATTR than did healthy volunteers and asymptomatic gene carriers (P<0.05). All 8 patients with higher antibody levels were late-onset cases. The ratio of wild-type TTR to ATTR V30M in serum from the high-antibody group was higher than that of the low-antibody group. ELISA results revealed two epitopes at positions 24–35 and 105–115 of ATTR V30M. We found a significant positive correlation between levels of the antibody at positions 24–35 and the age at FAP onset (r=0.751, P<0.05). An age-dependent increase in the occurrence of antibodies was observed in these patients with an epitope at positions 24–35.CONCLUSIONSThese findings may help explain the differences in early- and late-onset FAP and/or the progression of FAP.