JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

Author(s): Ya-jun Gu¹, Peng Ge^1;2, Yun Mu³, Jin-hai Lu¹, Fang Zheng¹, Xu-guo Sun¹
Affiliation(s): 1. School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China;2. Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China;3. Department of Clinical Laboratory, Tianjin Childrens Hospital, Tianjin 300074, China
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

Share this article to： More <<< Previous Paper \|Next Paper >>>

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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B1300046

@article{title="Clinical and laboratory characteristics of patients having amyloidogenic transthyretin deposition in osteoarthritic knee joints",
author="Ya-jun Gu, Peng Ge, Yun Mu, Jin-hai Lu, Fang Zheng, Xu-guo Sun",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B1300046"
}

%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
%P 92-99
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B1300046"

TY - JOUR
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
SP - 92
EP - 99
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B1300046"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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。

关键词组：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

References

[1] Altman,R, Asch,E, Bloch,D, 1986, Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee Arthritis Rheum, 29(8):1039-1049.

[2] Benito,M.J, Veale,D.J, FitzGerald,O, 2005, Synovial tissue inflammation in early and late osteoarthritis Ann Rheum Dis, 64(9):1263-1267.

[3] Christensen,H.E, Srenson,K.H, 1972, Local amyloid formation of capsula fibrosa in arthrosis coxae Acta Pathol Microbiol Scand Suppl, 233():128-131.

[4] Cortez,L.M, vila,C.L, Torres Bugeau,C.M, 2010, Glyceraldehyde-3-phosphate dehydrogenase tetramer dissociation and amyloid fibril formation induced by negatively charged membranes FEBS Lett, 584(3):625-630.

[5] Egan,M.S, Goldenberg,D.L, Cohen,A.S, 1982, The association of amyloid deposits and osteoarthritis Arthritis Rheum, 25(2):204-208.

[6] El Mansoury,T.M, Hazenberg,B.P.C, El Badawy,S.A, 2002, Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arthritis: clinical and laboratory characteristics Ann Rheum Dis, 61(1):42-47.

[7] Gorevic,P.D, Prelli,F.C, Wright,J, 1989, Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy J Clin Invest, 83(3):836-843.

[8] Hattori,T, Takei,Y, Koyama,J, 2003, Clinical and pathological studies of cardiac amyloidosis in transthyretin type familial amyloid polyneuropathy Amyloid, 10(4):229-239.

[9] Hurst,N.P, van den Berg,R, Disney,A, 1989, Dialysis related arthropathy: a survey of 95 patients receiving chronic haemodialysis with special reference to microglobulin related amyloidosis Ann Rheum Dis, 48(5):409-420.

[10] Ihse,E, Suhr,O.B, Hellman,U, 2011, Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis J Mol Med, 89(2):171-180.

[11] Insall,J.N, Dorr,L.D, Scott,R.D, 1989, Rationale of the Knee Society clinical rating system Clin Orthop Relat Res, 248():13-14.

[12] Kingsbury,J.S, Klimtchuk,E.S, Thberge,R, 2007, Expression, purification, and cysteine-10 modification of native sequence recombinant human transthyretin Protein Express Purif, 53(2):370-377.

[13] Kuroda,T, Tanabe,N, Sakatsume,M, 2002, Comparison of gastroduodenal, renal and abdominal fat biopsies for diagnosing amyloidosis in rheumatoid arthritis Clin Rheumatol, 21(2):123-128.

[14] Ladefoged,C, 1983, Amyloid in osteoarthritic hip joints: deposits in relation to chondromatosis, pyrophosphate, and inflammatory cell infiltrate in the synovial membrane and fibrous capsule Ann Rheum Dis, 42(6):659-664.

[15] M'Bapp,P, Grateau,G, 2012, Osteo-articular manifestations of amyloidosis Best Pract Res Clin Rheumatol, 26(4):459-475.

[16] Niggemeyer,O, Steinhagen,J, Deuretzbacher,G, 2011, Amyloid deposition in osteoarthritis of the hip Arch Orthop Trauma Surg, 131(5):637-643.

[17] Ray,A, Ray,B.K, 2008, An inflammation-responsive transcription factor in the pathophysiology of osteoarthritis Biorheology, 45(3-4):399-409.

[18] Sipe,J.D, Benson,M.D, Buxbaum,J.N, 2012, Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis Amyloid, 19(4):167-170.

[19] Solomon,A, Murphy,C.L, Kestler,D, 2006, Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I Arthritis Rheum, 54(11):3545-3550.

[20] Srenson,K.H, Christensen,H.E, 1973, Local amyloid formation in the hip joint capsule in osteoarthritis Acta Orthop Scand, 44(4):460-466.

[21] Tachibana,N, Tokuda,T, Yoshida,K, 1999, Usefulness of MALDUTOF mass spectrometry of immunoprecipitated serum variant transthyretin in the diagnosis of familial amyloid polyneuropathy Amyloid, 6(4):282-288.

[22] Torres-Bugeau,C.M, Borsarelli,C.D, Minahk,C.J, 2011, The key role of membranes in amyloid formation from a biophysical perspective Curr Protein Pept Sci, 12(3):166-180.

- Go to

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

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

References