Browse > Article
http://dx.doi.org/10.3345/kjp.2015.58.7.239

Complement regulation: physiology and disease relevance  

Cho, Heeyeon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Publication Information
Clinical and Experimental Pediatrics / v.58, no.7, 2015 , pp. 239-244 More about this Journal
Abstract
The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.
Keywords
Complement; Autoimmunity;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Jozsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol 2008;29:380-7.   DOI
2 Sethi S, Fervenza FC, Zhang Y, Smith RJ. Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3. Am J Kidney Dis 2012;60:316-21.   DOI
3 Mache CJ, Acham-Roschitz B, Fremeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedl S, et al. Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2009; 4:1312-6.   DOI
4 Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 2011;26:41-57.   DOI
5 Paixao-Cavalcante D, Hanson S, Botto M, Cook HT, Pickering MC. Factor H facilitates the clearance of GBM bound iC3b by controlling C3 activation in fluid phase. Mol Immunol 2009;46:1942-50.   DOI
6 Holers VM. The complement system as a therapeutic target in autoimmunity. Clin Immunol 2003;107:140-51.   DOI
7 Kim SJ, Kim J, Lee J, Cho SY, Kang HJ, Kim KY, et al. Intravitreal human complement factor H in a rat model of laser-induced choroidal neovascularisation. Br J Ophthalmol 2013;97:367-70.   DOI
8 Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2008;23:1957-72.   DOI
9 Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol 2009;9:729-40.   DOI
10 Sarma JV, Ward PA. The complement system. Cell Tissue Res 2011;343:227-35.   DOI
11 Zipfel PF, Heinen S, Jozsi M, Skerka C. Complement and diseases: defective alternative pathway control results in kidney and eye diseases. Mol Immunol 2006;43:97-106.   DOI
12 Cho HY, Lee BS, Moon KC, Ha IS, Cheong HI, Choi Y. Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate. Pediatr Nephrol 2007;22:874-80.   DOI
13 Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035-50.   DOI
14 Boon CJ, van de Kar NC, Klevering BJ, Keunen JE, Cremers FP, Klaver CC, et al. The spectrum of phenotypes caused by variants in the CFH gene. Mol Immunol 2009;46:1573-94.   DOI
15 Rodriguez de Cordoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sanchez-Corral P. The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 2004;41:355-67.   DOI
16 Kim DD, Song WC. Membrane complement regulatory proteins. Clin Immunol 2006;118:127-36.   DOI
17 Saland JM, Ruggenenti P, Remuzzi G; Consensus Study Group. Liver-kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 2009;20:940-9.   DOI
18 Lesher AM, Zhou L, Kimura Y, Sato S, Gullipalli D, Herbert AP, et al. Combination of factor H mutation and properdin deficiency causes severe C3 glomerulonephritis. J Am Soc Nephrol 2013; 24:53-65.   DOI
19 Blom AM, Villoutreix BO, Dahlback B. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system? Mol Immunol 2004;40:1333-46.   DOI
20 Jung S, Kang ES, Ki CS, Kim DW, Paik KH, Chang YS. Successful therapeutic plasma exchange in a 3.2-kg body weight neonate with atypical hemolytic uremic syndrome. J Clin Apher 2011;26: 162-5.   DOI
21 Haller W, Milford DV, Goodship TH, Sharif K, Mirza DF, McKiernan PJ. Successful isolated liver transplantation in a child with atypical hemolytic uremic syndrome and a mutation in complement factor H. Am J Transplant 2010;10:2142-7.   DOI
22 Lee BH, Kwak SH, Shin JI, Lee SH, Choi HJ, Kang HG, et al. Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency. Pediatr Res 2009;66:336-40.   DOI
23 Pickering M, Cook HT. Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 2011;20:271-7.   DOI
24 Lenderink AM, Liegel K, Ljubanovic D, Coleman KE, Gilkeson GS, Holers VM, et al. The alternative pathway of complement is activated in the glomeruli and tubulointerstitium of mice with adriamycin nephropathy. Am J Physiol Renal Physiol 2007; 293:F555-64.   DOI
25 Holers VM. The spectrum of complement alternative pathway-mediated diseases. Immunol Rev 2008;223:300-16.   DOI
26 Liew G, Mitchell P, Wong TY, Iyengar SK, Wang JJ. CKD increases the risk of age-related macular degeneration. J Am Soc Nephrol 2008;19:806-11.   DOI
27 Turnberg D, Lewis M, Moss J, Xu Y, Botto M, Cook HT. Complement activation contributes to both glomerular and tubulointerstitial damage in adriamycin nephropathy in mice. J Immunol 2006;177:4094-102.   DOI
28 Vernon KA, Cook HT. Complement in glomerular disease. Adv Chronic Kidney Dis 2012;19:84-92.   DOI
29 Sethi S, Fervenza FC, Zhang Y, Nasr SH, Leung N, Vrana J, et al. Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol 2011; 6:1009-17.   DOI
30 Bao L, Haas M, Quigg RJ. Complement factor H deficiency accelerates development of lupus nephritis. J Am Soc Nephrol 2011;22:285-95.   DOI
31 Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007;40:560-6.   DOI
32 Robson MG, Walport MJ. Pathogenesis of systemic lupus erythematosus (SLE). Clin Exp Allergy 2001;31:678-85.   DOI
33 Cook HT, Botto M. Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nat Clin Pract Rheumatol 2006;2:330-7.
34 Bao L, Haas M, Kraus DM, Hack BK, Rakstang JK, Holers VM, et al. Administration of a soluble recombinant complement C3 inhibitor protects against renal disease in MRL/lpr mice. J Am Soc Nephrol 2003;14:670-9.   DOI
35 Hsu SI, Couser WG. Chronic progression of tubulointerstitial damage in proteinuric renal disease is mediated by complement activation: a therapeutic role for complement inhibitors? J Am Soc Nephrol 2003;14(7 Suppl 2):S186-91.   DOI
36 Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol 2011;26:2085-8.   DOI
37 Schmidt CQ, Slingsby FC, Richards A, Barlow PN. Production of biologically active complement factor H in therapeutically useful quantities. Protein Expr Purif 2011;76:254-63.   DOI
38 Fakhouri F, de Jorge EG, Brune F, Azam P, Cook HT, Pickering MC. Treatment with human complement factor H rapidly reverses renal complement deposition in factor H-deficient mice. Kidney Int 2010;78:279-86.   DOI