Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
PLoS One. 2022 Mar 31;17(3):e0266092. doi: 10.1371/journal.pone.0266092. eCollection 2022.
We have previously shown that transthyretin (TTR) amyloidosis patients have amyloid fibrils of either of two compositions; type A fibrils consisting of large amounts of C-terminal TTR fragments in addition to full-length TTR, or type B fibrils consisting of only full-length TTR. Since type A fibrils are associated with an older age in ATTRVal30Met (p.Val50Met) amyloidosis patients, it has been discussed if the TTR fragments are derived from degradation of the amyloid deposits as the patients are aging. The present study aimed to investigate if the fibril composition type changes over time, especially if type B fibrils can shift to type A fibrils as the disease progresses.
Abdominal adipose tissue biopsies from 29 Swedish ATTRVal30Met amyloidosis patients were investigated. The fibril type in the patients´ initial biopsy taken for diagnostic purposes was compared to a biopsy taken several years later (ranging between 2 and 13 years). The fibril composition type was determined by western blot.
All 29 patients had the same fibril composition type in both the initial and the follow-up biopsy (8 type A and 21 type B). Even patients with a disease duration of more than 12 years and an age over 75 years at the time of the follow-up biopsy had type B fibrils in both biopsies.
The result clearly shows that the amyloid fibril composition containing large amounts of C-terminal fragments (fibril type A) is a consequence of other factors than a slow degradation process occurring over time.
我们之前已经表明，转甲状腺素蛋白（TTR）淀粉样变性患者的淀粉样纤维有两种组成类型；A 型纤维除全长 TTR 外还含有大量 C 端 TTR 片段，B 型纤维仅由全长 TTR 组成。由于 A 型纤维与 ATTRVal30Met（p.Val50Met）淀粉样变性患者的年龄较大有关，因此有人讨论了随着患者年龄的增长，TTR 片段是否是由淀粉样沉积物的降解产生的。本研究旨在探讨纤维组成类型是否随时间变化，特别是 B 型纤维是否可以随着疾病的进展转变为 A 型纤维。
研究了 29 名瑞典 ATTRVal30Met 淀粉样变性患者的腹部脂肪组织活检。将患者最初用于诊断目的的活检中的纤维类型与几年后（2 至 13 年之间）进行的活检进行比较。通过 Western blot 确定纤维组成类型。
29 名患者在初始和随访活检中均具有相同的纤维组成类型（8 型 A 和 21 型 B）。甚至在随访活检时疾病持续时间超过 12 年且年龄超过 75 岁的患者，在两次活检中均存在 B 型纤维。
结果清楚地表明，含有大量 C 端片段的淀粉样纤维组成（纤维类型 A）是其他因素的结果，而不是随着时间的推移发生的缓慢降解过程。
