Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

Complement regulation: physiology and disease relevance

  • Cho, Heeyeon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 투고 : 2015.04.28
  • 심사 : 2015.05.27
  • 발행 : 2015.07.10
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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.

키워드

참고문헌

  1. Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol 2009;9:729-40. https://doi.org/10.1038/nri2620
  2. Sarma JV, Ward PA. The complement system. Cell Tissue Res 2011;343:227-35. https://doi.org/10.1007/s00441-010-1034-0
  3. Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2008;23:1957-72. https://doi.org/10.1007/s00467-008-0872-4
  4. 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. https://doi.org/10.1016/j.molimm.2005.06.015
  5. 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. https://doi.org/10.1007/s00467-007-0438-x
  6. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 2011;26:41-57. https://doi.org/10.1007/s00467-010-1556-4
  7. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035-50. https://doi.org/10.1681/ASN.2004100861
  8. Jozsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol 2008;29:380-7. https://doi.org/10.1016/j.it.2008.04.008
  9. 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. https://doi.org/10.1016/j.molimm.2009.02.013
  10. 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. https://doi.org/10.1016/j.molimm.2004.02.005
  11. Kim DD, Song WC. Membrane complement regulatory proteins. Clin Immunol 2006;118:127-36. https://doi.org/10.1016/j.clim.2005.10.014
  12. 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. https://doi.org/10.1681/ASN.2012060570
  13. 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. https://doi.org/10.1016/j.molimm.2003.12.002
  14. 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. https://doi.org/10.1002/jca.20283
  15. 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. https://doi.org/10.1681/ASN.2008080906
  16. 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. https://doi.org/10.1111/j.1600-6143.2010.03228.x
  17. 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. https://doi.org/10.1203/PDR.0b013e3181b1bd4a
  18. Pickering M, Cook HT. Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 2011;20:271-7. https://doi.org/10.1097/MNH.0b013e328345848b
  19. 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. https://doi.org/10.1016/j.molimm.2009.03.030
  20. 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. https://doi.org/10.1053/j.ajkd.2012.04.011
  21. 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. https://doi.org/10.1152/ajprenal.00403.2006
  22. Holers VM. The spectrum of complement alternative pathway-mediated diseases. Immunol Rev 2008;223:300-16. https://doi.org/10.1111/j.1600-065X.2008.00641.x
  23. 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. https://doi.org/10.4049/jimmunol.177.6.4094
  24. Vernon KA, Cook HT. Complement in glomerular disease. Adv Chronic Kidney Dis 2012;19:84-92. https://doi.org/10.1053/j.ackd.2012.02.015
  25. 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. https://doi.org/10.2215/CJN.07110810
  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. https://doi.org/10.1681/ASN.2007080844
  27. Bao L, Haas M, Quigg RJ. Complement factor H deficiency accelerates development of lupus nephritis. J Am Soc Nephrol 2011;22:285-95. https://doi.org/10.1681/ASN.2010060647
  28. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007;40:560-6. https://doi.org/10.1080/08916930701510673
  29. Robson MG, Walport MJ. Pathogenesis of systemic lupus erythematosus (SLE). Clin Exp Allergy 2001;31:678-85. https://doi.org/10.1046/j.1365-2222.2001.01147.x
  30. 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.
  31. Holers VM. The complement system as a therapeutic target in autoimmunity. Clin Immunol 2003;107:140-51. https://doi.org/10.1016/S1521-6616(03)00034-2
  32. 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. https://doi.org/10.1097/01.ASN.0000051597.27127.A1
  33. 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. https://doi.org/10.1097/01.ASN.0000070032.58017.20
  34. 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. https://doi.org/10.1016/j.pep.2010.12.002
  35. 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. https://doi.org/10.1136/bjophthalmol-2012-302307
  36. 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. https://doi.org/10.1038/ki.2010.132
  37. 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. https://doi.org/10.1007/s00467-011-1989-4
  38. 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. https://doi.org/10.2215/CJN.01090209

피인용 문헌

  1. Serum mannose‐binding lectin levels after aneurysmal subarachnoid hemorrhage vol.134, pp.5, 2015, https://doi.org/10.1111/ane.12552
  2. CD59 polymorphisms are associated with gene expression and different sexual susceptibility to pemphigus foliaceus vol.50, pp.6, 2015, https://doi.org/10.1080/08916934.2017.1329830
  3. Kidney Transplantation in Patients with Atypical Hemolytic Uremic Syndrome due to Complement Factor H Deficiency: Impact of Liver Transplantation vol.33, pp.1, 2015, https://doi.org/10.3346/jkms.2018.33.e4
  4. The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy vol.10, pp.None, 2015, https://doi.org/10.3389/fimmu.2019.01074
  5. Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma vol.11, pp.None, 2020, https://doi.org/10.3389/fimmu.2020.01402