complement system proteins


Summary: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).

Top Publications

  1. Ricklin D, Lambris J. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013;190:3831-8 pubmed publisher
  2. Wu L, Tao Q, Chen W, Wang Z, Song Y, Sheng S, et al. Association between polymorphisms of complement pathway genes and age-related macular degeneration in a Chinese population. Invest Ophthalmol Vis Sci. 2013;54:170-4 pubmed publisher
    ..With the sample size of our study, no relationship was found for AMD and the two SNPs of C3. Gene variants in CFH and C2/CFB contribute to AMD in the Chinese population. ..
  3. Fremeaux Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon Durey M, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8:554-62 pubmed publisher
    ..Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background. ..
  4. Goicoechea de Jorge E, Caesar J, Malik T, Patel M, Colledge M, Johnson S, et al. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc Natl Acad Sci U S A. 2013;110:4685-90 pubmed publisher
    ..Our data demonstrate that these CFHR proteins function as competitive antagonists of CFH to modulate complement activation in vivo and explain why variation in the CFHRs predisposes to disease. ..
  5. Bresin E, Rurali E, Caprioli J, Sanchez Corral P, Fremeaux Bacchi V, Rodriguez de Cordoba S, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24:475-86 pubmed publisher
    ..Furthermore, screening patients with aHUS for all known disease-associated genes may inform decisions about kidney transplantation. ..
  6. Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, et al. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant. 2013;13:663-75 pubmed publisher
    ..07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies. ..
  7. Parker C. Paroxysmal nocturnal hemoglobinuria. Curr Opin Hematol. 2012;19:141-8 pubmed publisher
    ..Novel reagents that target the alternative pathway of complement C3 convertase are being developed with a goal of inhibiting both the extravascular and the intravascular hemolysis of PNH. ..
  8. Ioannou A, Dalle Lucca J, Tsokos G. Immunopathogenesis of ischemia/reperfusion-associated tissue damage. Clin Immunol. 2011;141:3-14 pubmed publisher
    ..Clinical trials that will determine the therapeutic value of each approach is needed. ..
  9. Pickering M, Cook H. Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens. 2011;20:271-7 pubmed publisher
    ..C5 inhibition appears to be effective therapy for aHUS. An important unresolved question is the role of C5 inhibition in C3 glomerulopathies. ..

More Information


  1. Ermini L, Goodship T, Strain L, Weale M, Sacks S, Cordell H, et al. Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS. Mol Immunol. 2012;49:640-8 pubmed publisher
    ..Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations. ..
  2. Gale D, Pickering M. Regulating complement in the kidney: insights from CFHR5 nephropathy. Dis Model Mech. 2011;4:721-6 pubmed publisher
    ..In this review, we discuss how studying CFHR5 nephropathy can contribute to our understanding of the role of complement in kidney diseases such as dense deposit disease, C3 glomerulonephritis and atypical haemolytic uraemic syndrome. ..
  3. Selman L, Hansen S. Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1). Immunobiology. 2012;217:851-63 pubmed publisher
    ..These findings suggest dual or overlapping functions of CL-11 in innate immunity and in fetal development. ..
  4. Tjomsland V, Ellegård R, Che K, Hinkula J, Lifson J, Larsson M. Complement opsonization of HIV-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families. PLoS ONE. 2011;6:e23542 pubmed publisher
  5. Oikonomopoulou K, Ricklin D, Ward P, Lambris J. Interactions between coagulation and complement--their role in inflammation. Semin Immunopathol. 2012;34:151-65 pubmed publisher
  6. Moll G, Jitschin R, von Bahr L, Rasmusson Duprez I, Sundberg B, Lonnies L, et al. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLoS ONE. 2011;6:e21703 pubmed publisher
    ..Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells. ..
  7. Degn S, Jensenius J, Thiel S. Disease-causing mutations in genes of the complement system. Am J Hum Genet. 2011;88:689-705 pubmed publisher
    ..Here, we compare the functional immunologic consequences of "conventional" complement deficiencies with these newly described developmental roles. ..
  8. Sethi S, Fervenza F, Zhang Y, Zand L, Vrana J, Nasr S, et al. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82:465-73 pubmed
    ..Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury. ..
  9. Sokolowski J, Mandell J. Phagocytic clearance in neurodegeneration. Am J Pathol. 2011;178:1416-28 pubmed publisher
    ..Because the regulation of phagocytic activity is intertwined with cytokine signaling, this review also addresses the relationships among CNS inflammation, glial responses, and phagocytic clearance. ..
  10. Molina Cruz A, DeJong R, Ortega C, Haile A, Abban E, Rodrigues J, et al. Some strains of Plasmodium falciparum, a human malaria parasite, evade the complement-like system of Anopheles gambiae mosquitoes. Proc Natl Acad Sci U S A. 2012;109:E1957-62 pubmed publisher
    ..Evasion of the A. gambiae immune system by P. falciparum may be the result of parasite adaptation to sympatric mosquito vectors and may be an important factor driving malaria transmission. ..
  11. Fett A, Hermann M, Muether P, Kirchhof B, Fauser S. Immunohistochemical localization of complement regulatory proteins in the human retina. Histol Histopathol. 2012;27:357-64 pubmed publisher
    ..Decreased and therefore unbalanced expression of regulators, as shown in this study for CFH and MCP, may ultimately lead to AMD. ..
  12. Reti M, Farkas P, Csuka D, Rázsó K, Schlammadinger A, Udvardy M, et al. Complement activation in thrombotic thrombocytopenic purpura. J Thromb Haemost. 2012;10:791-8 pubmed publisher
    ..These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance. ..
  13. Banz Y, Rieben R. Role of complement and perspectives for intervention in ischemia-reperfusion damage. Ann Med. 2012;44:205-17 pubmed publisher
  14. Li K, Fazekasova H, Wang N, Sagoo P, Peng Q, Khamri W, et al. Expression of complement components, receptors and regulators by human dendritic cells. Mol Immunol. 2011;48:1121-7 pubmed publisher
    ..It acts as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases. ..
  15. Sparrow J, Ueda K, Zhou J. Complement dysregulation in AMD: RPE-Bruch's membrane-choroid. Mol Aspects Med. 2012;33:436-45 pubmed publisher
    ..One recurring theme is the potential for disease promotion by diverse types of oxidation products. ..
  16. Yoshiya K, Lapchak P, Thai T, Kannan L, Rani P, Dalle Lucca J, et al. Depletion of gut commensal bacteria attenuates intestinal ischemia/reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2011;301:G1020-30 pubmed publisher
    ..These results suggest that depletion of gut commensal bacteria decreases B cells, Igs, and TLR expression in the intestine, inhibits complement activation, and attenuates intestinal inflammation and injury following M I/R. ..
  17. Servais A, Noel L, Roumenina L, Le Quintrec M, Ngo S, Dragon Durey M, et al. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82:454-64 pubmed publisher
    ..The localization of the C3 deposits may be under the influence of MCP expression. ..
  18. Happonen K, Heinegard D, Saxne T, Blom A. Interactions of the complement system with molecules of extracellular matrix: relevance for joint diseases. Immunobiology. 2012;217:1088-96 pubmed publisher
    ..Future challenges are to target the complement inhibition specifically to the joints to minimize systemic complement blockade...
  19. Tuo J, Grob S, Zhang K, Chan C. Genetics of immunological and inflammatory components in age-related macular degeneration. Ocul Immunol Inflamm. 2012;20:27-36 pubmed publisher
    ..We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD. ..
  20. Loirat C, Fremeaux Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60 pubmed publisher
    ..Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early. ..
  21. Khandhadia S, Cipriani V, Yates J, Lotery A. Age-related macular degeneration and the complement system. Immunobiology. 2012;217:127-46 pubmed publisher
    ..This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease. ..
  22. Athanasiou Y, Voskarides K, Gale D, Damianou L, Patsias C, Zavros M, et al. Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. Clin J Am Soc Nephrol. 2011;6:1436-46 pubmed publisher
    ..This larger patient cohort establishes the clinical course, significant variable expressivity, and marked gender difference regarding the development of CRF and ESRD. ..
  23. Skattum L, van Deuren M, van der Poll T, Truedsson L. Complement deficiency states and associated infections. Mol Immunol. 2011;48:1643-55 pubmed publisher
    ..The roles of complement in host defense against common infections are also discussed. ..
  24. Forneris F, Wu J, Gros P. The modular serine proteases of the complement cascade. Curr Opin Struct Biol. 2012;22:333-41 pubmed publisher
  25. Vu D, Wong T, Granoff D. Cooperative serum bactericidal activity between human antibodies to meningococcal factor H binding protein and neisserial heparin binding antigen. Vaccine. 2011;29:1968-73 pubmed publisher
    ..For meningococcal vaccines that target relatively sparsely exposed antigens such fHbp or NHba, non-bactericidal antibodies against individual antigens can cooperate and elicit SBA. ..
  26. Geerdink L, Westra D, van Wijk J, Dorresteijn E, Lilien M, Davin J, et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol. 2012;27:1283-91 pubmed publisher
    ..The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options. ..
  27. Westra D, Wetzels J, Volokhina E, van den Heuvel L, van de Kar N. A new era in the diagnosis and treatment of atypical haemolytic uraemic syndrome. Neth J Med. 2012;70:121-9 pubmed
  28. Bukreyev A, Yang L, Collins P. The secreted G protein of human respiratory syncytial virus antagonizes antibody-mediated restriction of replication involving macrophages and complement. J Virol. 2012;86:10880-4 pubmed publisher
    ..The present study demonstrated that effective antibody-mediated restriction in vivo, and the evasion of this restriction by sG, involves pulmonary macrophages and complement, but not neutrophils...
  29. Westra D, Vernon K, Volokhina E, Pickering M, van de Kar N, van den Heuvel L. Atypical hemolytic uremic syndrome and genetic aberrations in the complement factor H-related 5 gene. J Hum Genet. 2012;57:459-64 pubmed publisher
    ..The identified CFHR5 mutations require functional studies to determine their relevance to aHUS, but they might be candidates for an altered genetic profile predisposing to the disease. ..
  30. Oliveira G, Lieberman J, Barillas Mury C. Epithelial nitration by a peroxidase/NOX5 system mediates mosquito antiplasmodial immunity. Science. 2012;335:856-9 pubmed publisher
  31. Stoermer K, Morrison T. Complement and viral pathogenesis. Virology. 2011;411:362-73 pubmed publisher
    ..This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. ..
  32. Håvik B, Le Hellard S, Rietschel M, Lybæk H, Djurovic S, Mattheisen M, et al. The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia. Biol Psychiatry. 2011;70:35-42 pubmed publisher
    ..These data demonstrate a significant role of complement control-related genes in the etiology of schizophrenia and support disease mechanisms that involve the activity of immunity-related pathways in the brain. ..
  33. Biglarnia A, Nilsson B, Nilsson T, von Zur Mühlen B, Wagner M, Berne C, et al. Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation. Transpl Int. 2011;24:e61-6 pubmed publisher
    ..This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included. ..
  34. Bomback A, Smith R, Barile G, Zhang Y, Heher E, Herlitz L, et al. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol. 2012;7:748-56 pubmed publisher
    ..Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered. ..
  35. Cui W, Zhao Y, Shan C, Kong G, Hu N, Zhang Y, et al. HBXIP upregulates CD46, CD55 and CD59 through ERK1/2/NF-?B signaling to protect breast cancer cells from complement attack. FEBS Lett. 2012;586:766-71 pubmed publisher
    ..Interestingly, the knockdown of CD59 was able to block the HBXIP-enhanced breast tumor growth in animal. Thus, we conclude that HBXIP upregulates CD46, CD55 and CD59 through p-ERK1/2/NF-?B signaling to protect breast cancer from CDC. ..
  36. Hamad O, Bäck J, Nilsson P, Nilsson B, Ekdahl K. Platelets, complement, and contact activation: partners in inflammation and thrombosis. Adv Exp Med Biol. 2012;946:185-205 pubmed publisher
    ..Thus, in addition to their traditional role as initiators of secondary hemostasis, platelets also act as mediators and regulators of inflammation in thrombotic events. ..
  37. Yuan Y, Ren J, Wu X, Cao S, Li J. Exogenous C3 postpones complement exhaustion and confers organ protection in murine sepsis. J Surg Res. 2011;168:e87-94 pubmed publisher
    ..We demonstrated a consumptive depletion of complement components toward septic peritonitis. Exogenous C3 supplementation in early stage of sepsis is helpful to sustain C3 levels, with enhanced bacterial clearance and improved outcomes. ..
  38. Poolpol K, Gadner B, Neururer S, Mellmann A, Karch H, Orth D, et al. Do complement factor H 402Y and C7 M allotypes predispose to (typical) haemolytic uraemic syndrome?. Int J Immunogenet. 2011;38:383-7 pubmed publisher
  39. Mika A, Reynolds S, Mohlin F, Willis C, Swe P, Pickering D, et al. Novel scabies mite serpins inhibit the three pathways of the human complement system. PLoS ONE. 2012;7:e40489 pubmed publisher
    ..In summary, the SMSs were acting at several levels mediating overall inhibition of the complement system and thus we propose that they may protect scabies mites from complement-mediated gut damage...
  40. Hammerschmidt C, Hallström T, Skerka C, Wallich R, Stevenson B, Zipfel P, et al. Contribution of the infection-associated complement regulator-acquiring surface protein 4 (ErpC) to complement resistance of Borrelia burgdorferi. Clin Dev Immunol. 2012;2012:349657 pubmed publisher
  41. Li Y, Lin F. Mesenchymal stem cells are injured by complement after their contact with serum. Blood. 2012;120:3436-43 pubmed publisher
  42. Moon H, Jung S, Lee Y, Lee J. Anticomplement activity of various solvent extracts from Korea local Artemisia spp. Immunopharmacol Immunotoxicol. 2012;34:95-7 pubmed publisher
    ..montana chloroform extracts showed inhibitory activity against complement system with 50% inhibitory concentrations (IC??) values of 54.3 and 64.2??g/mL. This is the first report of anticomplement activity from Artemisia plants. ..
  43. Trouw L, Daha M. Role of complement in innate immunity and host defense. Immunol Lett. 2011;138:35-7 pubmed publisher
    ..Alterations in this balance and hence the function of complement, by influence of auto-antibodies, or genetic variants, may render the complement system into a harmful player in tissue damage and pathology. ..
  44. Salmon J, Heuser C, Triebwasser M, Liszewski M, Kavanagh D, Roumenina L, et al. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. PLoS Med. 2011;8:e1001013 pubmed publisher NCT00198068. ..
  45. WENGER M, Sattler U, Goldschmidt Clermont E, Segner H. 17Beta-estradiol affects the response of complement components and survival of rainbow trout (Oncorhynchus mykiss) challenged by bacterial infection. Fish Shellfish Immunol. 2011;31:90-7 pubmed publisher
    ..In conclusion, the results from this study suggest that estrogens are able to modulate immune parameters of trout with functional consequences on their ability to cope with pathogens. ..
  46. Carroll M, Sim R. Complement in health and disease. Adv Drug Deliv Rev. 2011;63:965-75 pubmed publisher
    ..g. ischemic stroke). Insufficient complement activity is associated with susceptibility to infection (mainly bacterial) and development of autoimmune disease, like SLE (systemic lupus erythematosus). ..
  47. Giuntini S, Reason D, Granoff D. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding. Infect Immun. 2011;79:3751-9 pubmed publisher
    ..The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity. ..
  48. Weismann D, Hartvigsen K, Lauer N, Bennett K, Scholl H, Charbel Issa P, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature. 2011;478:76-81 pubmed publisher
    ..Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases. ..
  49. Mika A, Goh P, Holt D, Kemp D, Fischer K. Scabies mite peritrophins are potential targets of human host innate immunity. PLoS Negl Trop Dis. 2011;5:e1331 pubmed publisher
    ..Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement...
  50. Roumenina L, Loirat C, Dragon Durey M, Halbwachs Mecarelli L, Sautes Fridman C, Fremeaux Bacchi V. Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods. 2011;365:8-26 pubmed publisher
    ..Finally, we will discuss how the therapy of aHUS patients can be modified according to the functional consequences of each particular genetic defect. ..
  51. Dheilly N, Raftos D, Haynes P, Smith L, Nair S. Shotgun proteomics of coelomic fluid from the purple sea urchin, Strongylocentrotus purpuratus. Dev Comp Immunol. 2013;40:35-50 pubmed publisher
    ..However, based on this dataset, the expression of TLRs, NLRs and fibrinogen domain containing proteins in coelomic fluid and coelomocytes could not be verified...
  52. Baig N, Taylor R, Lindorfer M, Church A, LaPlant B, Pettinger A, et al. Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia. J Immunol. 2014;192:1620-9 pubmed publisher
  53. Noris M, Remuzzi G. Glomerular Diseases Dependent on Complement Activation, Including Atypical Hemolytic Uremic Syndrome, Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy: Core Curriculum 2015. Am J Kidney Dis. 2015;66:359-75 pubmed publisher