期刊首页 优先出版 当期阅读 过刊浏览 作者中心 关于期刊 English

《工程(英文)》 >> 2022年 第10卷 第3期 doi: 10.1016/j.eng.2020.08.018

血清淀粉样蛋白各亚型在类风湿性关节炎发病机制中的作用

a State Key Laboratory of Quality Research in Chinese Medicine & Macau Institute for Applied Research in Medicine and Health & Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China
b Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

# These authors contributed equally to this work.

收稿日期: 2020-05-05 修回日期: 2020-08-04 录用日期: 2020-08-21 发布日期: 2020-12-10

下一篇 上一篇

摘要

继发性淀粉样变性是一种致命的并发症。当急性或慢性感染同时伴有血清淀粉样蛋白A 1(serum amyloid A 1, SAA1)分泌过多并在内脏器官积聚时,可诱发淀粉样变性。前期研究通过全外显子组测序,在类风湿性关节炎(rheumatoid arthritis, RA)患者中发现一种新的致病突变发生在SAA1.2 的序列中。然而,SAA1 在RA发病及诱发并发症方面的机制仍不清楚。本研究的目的是确定SAA1 蛋白亚型在RA进展中的致病机制。实验将载有SAA1.2 突变位点等位基因的重组腺病毒载体adSAA1.2 转染C57 小鼠膝关节,并以adSAA1.3 和adSAA1.5 作为对照。应用微型计算机断层扫描(micro-CT)技术来确定骨形态和骨密度的变化。采用免疫组化学(IHC)分析、流式细胞术、酶联免疫吸附试验(ELISA)、实时聚合酶链反应(RT-PCR)等方法研究adSAA1.2 诱导的膝关节炎症和骨破坏过程中的疾病进展及细胞因子改变。结果发现,SAA1.2 转染导致膝关节发生关节炎和血清SAA1 蛋白含量增加(可诱发炎症反应),最终导致CD8+T 细胞激活和炎性细胞因子[包括白细胞介素(IL)-6、IL-22、基质金属蛋白酶(MMP)-3、MMP-9]水平升高,并伴有滑膜炎症和骨破坏。这些结果提示SAA1 蛋白不同亚型,尤其是SAA1.2 在RA的诱导和进展中发挥着重要作用,可能在RA的早期诊断和预后中具有重要价值。

补充材料

图片

图1

图2

图3

图4

图5

图6

图7

图8

参考文献

[ 1 ] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365(23):2205–19. 链接1

[ 2 ] Lu J, Yu Y, Zhu I, Cheng Y, Sun PD. Structural mechanism of serum amyloid Amediated inflammatory amyloidosis. Proc Natl Acad Sci USA 2014;111 (14):5189–94. 链接1

[ 3 ] Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009;27 (21):3437–44. 链接1

[ 4 ] Paret C, Schön Z, Szponar A, Kovacs G. Inflammatory protein serum amyloid A1 marks a subset of conventional renal cell carcinomas with fatal outcome. Eur Urol 2010;57(5):859–66. 链接1

[ 5 ] Sethi S, Vrana JA, Theis JD, Leung N, Sethi A, Nasr SH, et al. Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis. Kidney Int 2012;82(2):226–34. 链接1

[ 6 ] Zewinger S, Drechsler C, Kleber ME, Dressel A, Riffel J, Triem S, et al. Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk. Eur Heart J 2015;36(43):3007–16. 链接1

[ 7 ] Nakamura T, Higashi S, Tomoda K, Tsukano M, Baba S, Shono M. Significance of SAA1.3 allele genotype in Japanese patients with amyloidosis secondary to rheumatoid arthritis. Rheumatology 2006;45(1):43–9. 链接1

[ 8 ] Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann RheumDis 2014;73(7):1316–22. 链接1

[ 9 ] Kuo CF, Grainge MJ, Valdes AM, See LC, Yu KH, Shaw SWS, et al. Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study. Rheumatology 2017;56(6):928–33. 链接1

[10] Smolen JS, Aletaha D, Redlich K. The pathogenesis of rheumatoid arthritis: new insights from old clinical data? Nat Rev Rheumatol 2012;8(4):235–43. 链接1

[11] Li Y, Leung ELH, Pan H, Yao X, Huang Q, Wu M, et al. Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing. Oncotarget 2017;8(67):111119–29. 链接1

[12] Sun L, Ye RD. Serum amyloid A1: structure, function and gene polymorphism. Gene 2016;583(1):48–57. 链接1

[13] Yamada T, Okuda Y, Takasugi K, Itoh K, Igari J. Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis. Ann Rheum Dis 2001;60 (2):124–7. 链接1

[14] Connolly M, Veale DJ, Fearon U. Acute serum amyloid A regulates cytoskeletal rearrangement, cell matrix interactions and promotes cell migration in rheumatoid arthritis. Ann Rheum Dis 2011;70(7):1296–303. 链接1

[15] Yamada T, Wada A. Slower clearance of human SAA1.5 in mice: implications for allele specific variation of SAA concentration in human. Amyloid 2003;10 (3):147–50. 链接1

[16] Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA 2015;313(19):1973–4. 链接1

[17] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62(9):2569–81. 链接1

[18] Xu Y, Ikeda S, Sumida K, Yamamoto R, Tanaka H, Minato N. Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells. Nat Commun 2018;9(1):914. 链接1

[19] Wehrens EJ, Prakken BJ, van Wijk F. T cells out of control—impaired immune regulation in the inflamed joint. Nat Rev Rheumatol 2013;9(1):34–42. 链接1

[20] Sano T, Huang W, Hall JA, Yang Y, Chen A, Gavzy SJ, et al. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 2015;163(2):381–93. 链接1

[21] Kinne RW, Stuhlmüller B, Burmester GR. Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res Ther 2007;9(6):224. 链接1

[22] Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1b and 6 but not transforming growth factor-b are essential for the differentiation of interleukin 17—producing human T helper cells. Nat Immunol 2007;8 (9):942–9. 链接1

[23] Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001;344(12):907–16. 链接1

[24] Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor a in rheumatoid arthritis. Arthritis Rheum 1995;38 (2):151–60. 链接1

[25] LeJan S, Plée J, Vallerand D, Dupont A, Delanez E, Durlach A, et al. Innate immune cell-produced IL-17 sustains inflammation in bullous pemphigoid. J Invest Dermatol 2014;134(12):2908–17. 链接1

[26] Bouta EM, Bell RD, Rahimi H, Xing L, Wood RW, Bingham CO, et al. Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. Nat Rev Rheumatol 2018;14(2):94–106. 链接1

[27] Joss N, McLaughlin K, Simpson K, Boulton-Jones JM. Presentation, survival and prognostic markers in AA amyloidosis. QJM 2000;93(8):535–42. 链接1

[28] Wakhlu A, Krisnani N, Hissaria P, Aggarwal A, Misra R. Prevalence of secondary amyloidosis in Asian North Indian patients with rheumatoid arthritis. J Rheumatol 2003;30(5):948–51. 链接1

[29] Chen M, Zhou H, Cheng N, Qian F, Ye RD. Serum amyloid A1 isoforms display different efficacy at Toll-like receptor 2 and formyl peptide receptor 2. Immunobiology 2014;219(12):916–23. 链接1

[30] Asquith DL, Miller AM, McInnes IB, Liew FY. Animal models of rheumatoid arthritis. Eur J Immunol 2009;39(8):2040–4. 链接1

[31] Toh ML, Hong SS, van de Loo F, Franqueville L, Lindholm L, van den Berg W, et al. Enhancement of adenovirus-mediated gene delivery to rheumatoid arthritis synoviocytes and synovium by fiber modifications: role of arginine– glycine–aspartic acid (RGD)- and non-RGD-binding integrins. J Immunol 2005;175(11):7687–98. 链接1

[32] Feng ZY, He ZN, Zhang B, Li YQ, Guo J, Xu YL, et al. Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis. Cell TissueRes 2015;362(1):187–99. 链接1

[33] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007;7(6):429–42. 链接1

[34] Weyand CM. New insights into the pathogenesis of rheumatoid arthritis. Rheumatology 2000;39(Suppl 1):3–8. 链接1

[35] Smeets TJ, Kraan MC, Galjaard S, Youssef PP, Smith MD, Tak PP. Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage–pannus junction in patients with RA. Ann Rheum Dis 2001;60(6):561–5. 链接1

[36] Goodson N, Marks J, Lunt M, Symmons D. Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis 2005;64(11):1595–601. 链接1

相关研究