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                          補體系統-藥物開發和臨床研究熱點

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

Euro Diagnostica補體功能檢測試劑盒優勢

1)ELISA檢測方法-三種激活途徑，相同的檢測程序。

2)2005年上市，穩定的檢測系統。

3）反映真實的體內補體水平。

4）3小時內出結果，快速、準確。

5）靈活性強-可以適應個性的化操作流程。

6）適合自動化檢測系統檢測（Dynex, DS2,DSX）

7) 與溶血試驗（CH50, APH50）檢測結果一致。

8）性能穩定，文獻引用廣

9）CE認證，可同時用于臨床和科研檢測。

Euro Diagnostica試劑盒應用實例:

1）藥物開發-補體靶向治療

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

2）臨床研究-補體功能/活性監測

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

3）補體脫靶反應

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

訂購信息

應用文獻：

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.