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CLC number: R684.3

On-line Access: 2014-01-04

Received: 2013-02-09

Revision Accepted: 2013-07-29

Crosschecked: 2013-12-17

Cited: 5

Clicked: 5597

Citations:  Bibtex RefMan EndNote GB/T7714

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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.1 P.92-99

http://doi.org/10.1631/jzus.B1300046


Clinical and laboratory characteristics of patients having amyloidogenic transthyretin deposition in osteoarthritic knee joints


Author(s):  Ya-jun Gu1, Peng Ge1,2, Yun Mu3, Jin-hai Lu1, Fang Zheng1, Xu-guo Sun1

Affiliation(s):  1. School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China; more

Corresponding email(s):   zf172984@aliyun.com.cn

Key Words:  Amyloid, Immunoglobulin light chain, Matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry (MALDI-TOF MS), Osteoarthritis, Transthyretin


Ya-jun Gu, Peng Ge, Yun Mu, Jin-hai Lu, Fang Zheng, Xu-guo Sun. Clinical and laboratory characteristics of patients having amyloidogenic transthyretin deposition in osteoarthritic knee joints[J]. Journal of Zhejiang University Science B, 2014, 15(1): 92-99.

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author="Ya-jun Gu, Peng Ge, Yun Mu, Jin-hai Lu, Fang Zheng, Xu-guo Sun",
journal="Journal of Zhejiang University Science B",
volume="15",
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publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300046"
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%0 Journal Article
%T Clinical and laboratory characteristics of patients having amyloidogenic transthyretin deposition in osteoarthritic knee joints
%A Ya-jun Gu
%A Peng Ge
%A Yun Mu
%A Jin-hai Lu
%A Fang Zheng
%A Xu-guo Sun
%J Journal of Zhejiang University SCIENCE B
%V 15
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%P 92-99
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%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300046

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T1 - Clinical and laboratory characteristics of patients having amyloidogenic transthyretin deposition in osteoarthritic knee joints
A1 - Ya-jun Gu
A1 - Peng Ge
A1 - Yun Mu
A1 - Jin-hai Lu
A1 - Fang Zheng
A1 - Xu-guo Sun
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 1
SP - 92
EP - 99
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1300046


Abstract: 
Objective: Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods: Synovial membranes were obtained from 36 patients with knee osteoarthritis (OA) who underwent joint replacement surgery. From this sample, the diagnosis of amyloid was determined by Congo red staining, which demonstrated apple-green birefringence under a polarized microscope. All synovial membranes were immunohistochemically characterized for the expressions of amyloid immunoglobulin light chain (AL-κ and AL-λ), serum amyloid-A (SAA), amyloidogenic transthyretin (ATTR), and amyloidogenic β2-microglobulin (Aβ2M). matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry (MALDI-TOF MS) was used to analyze transthyretin (TTR) isoforms in the serum of each patient. Results: Nine cases (25%) were found to be amyloid-positive. Immunohistochemically, eight cases (88.9%) had ATTR deposition, and one sample (11.1%) was shown to be AL-κ-positive. MALDI-TOF MS identified that the TTR in the serum of the patients was unmodified wild-type TTR, TTR-Cys-S-S-Cys, and TTR-Cys-S-S-CysGly. The age at surgery and the disease duration were significantly higher in the ATTR-positive group than in the ATTR-negative group. Knee score and function score were significantly lower in the ATTR-positive group than in the ATTR-negative group. Conclusions: amyloid deposition in synovial membranes of OA patients was found to be ATTR and AL-κ. TTR in the serum of the patients was unmodified wild-type TTR together with two isoforms. The high age at surgery, long disease duration, and a deteriorated knee function were associated with ATTR amyloid deposition in the osteoarthritic knee joints.

伴发ATTR型淀粉样沉积的骨关节炎患者的临床和生物学特征分析

研究目的:旨在检测骨关节炎患者是否存在淀粉样变,分析淀粉样沉积的类型,并进一步研究与淀粉样沉积相关的临床和生物学指标。
创新方法:首次发现了骨关节炎淀粉样沉积相关的临床和生物学指标,为研究骨关节炎的发生机制提供了科学依据。
研究手段:收集36例接受关节置换术的骨关节炎患者的滑膜组织,利用刚果红染色结合偏振光显微镜鉴定滑膜组织是否发生淀粉样变沉积,并用免疫组化染色确定淀粉样变沉积蛋白的类型。最后用基质辅助激光解析电离飞行时间质谱检测血液中TTR基因突变的类型。
重要结论:在36例接受关节置换术的骨关节炎患者中,9例(25%)出现了淀粉样沉积,其中8例为ATTR相关的淀粉样变,1例与AL-κ相关。基质辅助激光解析电离飞行时间质谱显示(见图3),ATTR为野生型和修饰型蛋白,未发现突变的ATTR亚型。患者年龄和病程与ATTR淀粉样变呈正相关,膝关节评分和功能评分与ATTR淀粉样变呈负相关。因此,高龄、长病程、膝关节功能较差的骨关节炎患者可能同时伴发ATTR淀粉样沉积。在常规诊疗的同时,对于该类患者应给予足够重视,适当开展个体化治疗。

关键词:免疫球蛋白轻链;质谱;骨关节炎;淀粉样变;转甲状腺素蛋白(ATTR)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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