Suhr O B, Ando Y, Ohlsson P I, Olofsson A, Andersson K, Lundgren E, Ando M, Holmgren G
Department of Medicine, Umeå University Hospital, Sweden.
Eur J Clin Invest. 1998 Aug;28(8):687-92. doi: 10.1046/j.1365-2362.1998.00345.x.
For all forms of amyloidosis, the amyloid-generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS) discloses both thiol-conjugated and -unconjugated forms of wild-type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease.
Plasma from 35 individuals (12 symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI-MS.
The total TTR concentration was significantly lower in symptomatic TTR Met-30 carriers than in control subjects. An increased percentage of conjugated TTR Met-30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild-type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30 carriers.
The finding of a decreased ratio of unconjugated to conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.
对于所有形式的淀粉样变性，淀粉样蛋白生成机制尚不清楚。I型家族性淀粉样多神经病由变体转甲状腺素蛋白（TTR Met-30）引起。由于电喷雾电离质谱（ESI-MS）可揭示野生型和变体TTR的硫醇共轭形式和非共轭形式，我们想要研究TTR共轭与临床显性淀粉样疾病之间的关系。
使用ESI-MS分析了35名个体（12名有症状的TTR Met-30携带者、9名无症状者和14名健康对照者）的血浆。
有症状的TTR Met-30携带者的总TTR浓度显著低于对照者。与无症状者相比，有症状携带者中TTR Met-30的共轭百分比增加，而对照者、无症状者和有症状的TTR Met-30携带者的野生型TTR共轭百分比相似。
在有症状的TTR Met-30携带者的血浆样本中，未共轭与共轭的TTR Met-30比例降低，这一发现表明TTR的硫醇共轭可能参与淀粉样蛋白的形成。
