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                          補體系統(tǒng)-藥物開發(fā)和臨床研究熱點

補體系統(tǒng)是由35種廣泛存在于血清、組織液和細(xì)胞膜具有酶活性的蛋白質(zhì)組成的反應(yīng)系統(tǒng)。補體激活有三種途徑：1)經(jīng)典途徑2）旁路途徑3）凝集素反應(yīng)/MBL途徑。補體系統(tǒng)可通過這3條既相對獨立又相互聯(lián)系的途徑被激活，從而發(fā)揮調(diào)理吞噬、裂解細(xì)胞、介導(dǎo)炎癥、免疫調(diào)節(jié)和清除免疫復(fù)合物等多種生物學(xué)效應(yīng)，包括增強吞噬作用，增強吞噬細(xì)胞的趨化性；增加血管的通透性；中和病毒；細(xì)胞溶解作用；免疫反應(yīng)的調(diào)節(jié)作用等。補體系統(tǒng)在抗感染和自身免疫及其他疾病的發(fā)展過程中發(fā)揮重要作用。

Euro Diagnostica補體功能檢測試劑盒優(yōu)勢

1)ELISA檢測方法-三種激活途徑，相同的檢測程序。

2)2005年上市，穩(wěn)定的檢測系統(tǒng)。

3）反映真實的體內(nèi)補體水平。

4）3小時內(nèi)出結(jié)果，快速、準(zhǔn)確。

5）靈活性強-可以適應(yīng)個性的化操作流程。

6）適合自動化檢測系統(tǒng)檢測（Dynex, DS2,DSX）

7) 與溶血試驗（CH50, APH50）檢測結(jié)果一致。

8）性能穩(wěn)定，文獻(xiàn)引用廣

9）CE認(rèn)證，可同時用于臨床和科研檢測。

Euro Diagnostica試劑盒應(yīng)用實例:

1）藥物開發(fā)-補體靶向治療

研究表明,炎性疾病的發(fā)生、發(fā)展同補體的活化有關(guān)。因此,如何干擾和抑制補體活化產(chǎn)生的有害作用,成為藥理學(xué)研究的焦點之一，Euro Diagnostica試劑盒用于評估補體靶向治療效果（參考文獻(xiàn)4-8）。

2）臨床研究-補體功能/活性監(jiān)測

補體功能的評估在補體相關(guān)疾病的發(fā)生和治療中具有重要意義。文獻(xiàn)5-9 用Euro Diagnostica試劑盒監(jiān)測補體疾病治療中補體水平。

3）補體脫靶反應(yīng)

在某些情況下，補體激活可引起嚴(yán)重反應(yīng)，比如候選藥物的脫靶反應(yīng)，抗體依賴的補體激活，移植排斥反應(yīng)。（（參考文獻(xiàn)12-13）。）

訂購信息

應(yīng)用文獻(xiàn)：

1.Ricklin D and Lambris JD. Complement in Immune and Inflammatory Disorders:Therapeutic Interventions. J Immunol 2013; 190: 3839-3847

2. Seelen MA et al. Functional analysis of the classical, alternative, and MBL pathways of

the complement system: standardization and validation of a simple ELISA. J Immunol Meth 2005; 296: 187–198

3. Salvesen B and Mollnes TE. Pathway-specific complement activity in pigs evaluated with a human functional complement assay. Mol Imm 2009;6:1620-1625

4.Hill A et al. A Subcutaneously Administered Investigational RNAi Therapeutic (ALN-CC5) Targeting Complement C5 for Treatment of PNH and Complement-Mediated Diseases: Interim Phase 1 Study Results. Abstract 2413 ;58th ASH Annual Meeting 2015

5. Jore MM et al. Structural basis for therapeutic inhibition of complement C5. Nature Structural & Molecular Biology 2016: doi:10.1038/nsmb.3196

6. Würzner R et al. Assessment of complement activity by ELISA. Abstract #41 16th Biennial Meeting of the European Society for Immunodeficiencies, ESID 2014

7. Kocsis A. Selective Inhibition of the Lectin Pathway of Complement with

Phage Display Selected Peptides against Mannose-Binding Lectin-Associated Serine

Protease (MASP)-1 and -2: Significant Contribution of MASP-1 to Lectin Pathway

Activation. J of Immunol 2010;185: 4169–4178

8. Kadam A P and Sahu A Identification of Complin, a Novel Complement Inhibitor that Targets Complement Proteins Factor B and C2. J of Immunol 2010;184: 7116-24

9. Volokhina E B et al. Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome. Clin Immunol 2015; 160: 237–43

10. Heinen S et al. Monitoring and modeling treatment of atypical hemolytic uremic

syndrome. Molecular Immunology 2013; 54:84– 88

11. Hallenstensen RF et al. Eculizumab treatment during pregnancy does not affect the

complement system activity of the newborn. Immunobiology 2015; 220:452–459

12. Castellano G et al. Therapeutic Targeting of Classical and Lectin Pathways of Complement Protects from Ischemia-Reperfusion- Induced Renal Damage. Am J Pathol 2010; 176:1648–1659

13. Brennan FR et al. Safety and immunotoxicity assessment of immunomodulatory

monoclonal antibodies. mAbs 2010; 2:3, 233-255

14. Mitsuru Sugimoto,etal.Possible participation of IgG4 in the activation of complement in IgG4-related disease with  hypocomplementemia.Modern Rheumatology,Volume 26, 2016 - Issue 2

15．Y. Palarasah,etal.Novel assays to assess the functional capacity of the classical, the alternative and the lectin pathways of the complement system.Clincal&Experimental Immunology,Volume164, Issue3,June 2011,Pages 388-395.