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患有淀粉样变性转甲状腺素蛋白沉积的骨关节炎膝关节患者的临床和实验室特征。

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

机构信息

School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China; Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Department of Clinical Laboratory, Tianjin Children's Hospital, Tianjin 300074, China.

出版信息

J Zhejiang Univ Sci B. 2014 Jan;15(1):92-9. doi: 10.1631/jzus.B1300046.

DOI:10.1631/jzus.B1300046
PMID:24390749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3891123/
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.

摘要

目的

本研究旨在探讨膝关节淀粉样变性的骨关节炎(OA)患者的临床和实验室特征。

方法

从 36 例行膝关节置换术的 OA 患者的滑膜组织中获取样本。通过刚果红染色确定淀粉样变的诊断,偏光显微镜下可见苹果绿双折射。所有滑膜组织均通过免疫组织化学方法检测淀粉样免疫球蛋白轻链(AL-κ 和 AL-λ)、血清淀粉样 A(SAA)、淀粉样变性转甲状腺素(ATTR)和淀粉样变性β2-微球蛋白(Aβ2M)的表达。采用基质辅助激光解吸电离/飞行时间质谱(MALDI-TOF MS)分析每位患者血清中转甲状腺素(TTR)的异构体。

结果

9 例(25%)为阳性。免疫组织化学结果显示,8 例(88.9%)存在 ATTR 沉积,1 例(11.1%)为 AL-κ 阳性。MALDI-TOF MS 鉴定患者血清中的 TTR 为未修饰野生型 TTR、TTR-Cys-S-S-Cys 和 TTR-Cys-S-S-CysGly。ATTR 阳性组的手术年龄和疾病持续时间明显高于 ATTR 阴性组。ATTR 阳性组的膝关节评分和功能评分明显低于 ATTR 阴性组。

结论

OA 患者滑膜中的淀粉样沉积物为 ATTR 和 AL-κ。患者血清中的 TTR 为未修饰野生型 TTR 及其两种异构体。手术年龄高、疾病持续时间长和膝关节功能恶化与 OA 膝关节中的 ATTR 淀粉样沉积有关。

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