complement c1 inactivator proteins


Summary: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.

Top Publications

  1. Faiyaz Ul Haque M, Al Gazlan S, Abalkhail H, Al Abdulatif A, Toulimat M, Peltekova I, et al. Novel and recurrent mutations in the C1NH gene of Arab patients affected with hereditary angioedema. Int Arch Allergy Immunol. 2010;151:149-54 pubmed publisher
    ..We conclude that the spectrum of C1NH gene mutations in HAE patients is wider due to the likely presence of novel and recurrent mutations in patients of other ethnicities. ..
  2. Bork K, Meng G, Staubach P, Hardt J. Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema. Transfusion. 2005;45:1774-84 pubmed
    ..C1 inhibitor concentrate is highly effective and safe in treating abdominal attacks in patients suffering from hereditary angioedema. ..
  3. Roche O, Blanch A, Duponchel C, Fontan G, Tosi M, Lopez Trascasa M. Hereditary angioedema: the mutation spectrum of SERPING1/C1NH in a large Spanish cohort. Hum Mutat. 2005;26:135-44 pubmed
    ..This is the first evidence of SERPING1/C1NH mutations in coding regions that differ from the canonical splice sites that affect splicing, which suggests the presence of an exonic splicing enhancer (ESE) in exon 5. ..
  4. Bork K, Hardt J, Staubach Renz P, Witzke G. Risk of laryngeal edema and facial swellings after tooth extraction in patients with hereditary angioedema with and without prophylaxis with C1 inhibitor concentrate: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:58-64 pubmed publisher
    ..Short-term prophylaxis with C1 inhibitor concentrate significantly reduces the risk of HAE-C1-INH symptoms after tooth extraction. In some patients, however, facial swellings and laryngeal edema symptoms may occur despite prophylaxis. ..
  5. Agostoni A, Aygören Pürsün E, Binkley K, Blanch A, Bork K, Bouillet L, et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114:S51-131 pubmed
    ..This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. ..
  6. Lathem W, Bergsbaken T, Welch R. Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7. J Exp Med. 2004;199:1077-87 pubmed publisher
    ..These data suggest that by recruiting C1-INH to cell surfaces, StcE may protect both E. coli O157:H7 and the host cells to which the bacterium adheres from complement-mediated lysis and potentially damaging inflammatory events...
  7. Li M, Wen F, Zuo C, Zhang X, Chen H, Huang S, et al. SERPING1 polymorphisms in polypoidal choroidal vasculopathy. Mol Vis. 2010;16:231-9 pubmed
    ..To investigate whether common genetic variants in the complement component 1 inhibitor gene (serpin peptidase inhibitor, clade G, member 1, SERPING1) are associated with polypoidal choroidal vasculopathy (PCV) in a Chinese Han population...
  8. Zuraw B. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359:1027-36 pubmed publisher
  9. Cumming S, Halsall D, Ewan P, Lomas D. The effect of sequence variations within the coding region of the C1 inhibitor gene on disease expression and protein function in families with hereditary angio-oedema. J Med Genet. 2003;40:e114 pubmed

More Information


  1. Pappalardo E, Zingale L, Terlizzi A, Zanichelli A, Folcioni A, Cicardi M. Mechanisms of C1-inhibitor deficiency. Immunobiology. 2002;205:542-51 pubmed
    ..Such conditions, as extensively investigated in sepsis, are of great relevance because they open the possibility of using C1-Inh as therapeutic agent in several different diseases. ..
  2. Murray Rust T, Kerr F, Thomas A, Wu T, Yongqing T, Ong P, et al. Modulation of the proteolytic activity of the complement protease C1s by polyanions: implications for polyanion-mediated acceleration of interaction between C1s and SERPING1. Biochem J. 2009;422:295-303 pubmed publisher
    ..Thus, whereas polyanions are able to bind C1s and modulate its activity, polyanion interactions with SERPING1 must also play a vital role in the mechanism by which these cofactors accelerate the C1s-SERPING1 reaction. ..
  3. Wahn V, Aberer W, Eberl W, Faßhauer M, Kuhne T, Kurnik K, et al. Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies. Eur J Pediatr. 2012;171:1339-48 pubmed publisher
  4. Duponchel C, Djenouhat K, Fremeaux Bacchi V, Monnier N, Drouet C, Tosi M. Functional analysis of splicing mutations and of an exon 2 polymorphic variant of SERPING1/C1NH. Hum Mutat. 2006;27:295-6 pubmed
    ..The latter finding suggests that mutations affecting splicing of exon 2 of the SERPING1/C1NH gene may have different consequences in monocytes versus other cell types. ..
  5. Gompels M, Lock R, Abinun M, Bethune C, Davies G, Grattan C, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139:379-94 pubmed
    ..Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification. ..
  6. Blanch A, Roche O, Lopez Granados E, Fontan G, Lopez Trascasa M. Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations. Hum Mutat. 2002;20:405-6 pubmed
    ..Seven of these families had no history of the disease, and in five of them we were able to verify that the progenitors did not have the mutation. Therefore, they were de novo mutations. ..
  7. Weis M. Clinical review of hereditary angioedema: diagnosis and management. Postgrad Med. 2009;121:113-20 pubmed publisher
    ..Nevertheless, diagnosis may be delayed by 2 decades. We review available therapies and clinical characteristics that will both help clinicians diagnose HAE and distinguish among emergencies and nonemergency cases. ..
  8. Bergamaschini L, Gobbo G, Gatti S, Caccamo L, Prato P, Maggioni M, et al. Endothelial targeting with C1-inhibitor reduces complement activation in vitro and during ex vivo reperfusion of pig liver. Clin Exp Immunol. 2001;126:412-20 pubmed
    ..These results suggest that adding C1-INH to the preservation solution may be useful to reduce complement activation and tissue injury during the reperfusion of an ischaemic liver. ..
  9. Kesim B, Uyguner Z, Gelincik A, Mete Gökmen N, Sin A, Karakaya G, et al. The Turkish Hereditary Angioedema Pilot Study (TURHAPS): the first Turkish series of hereditary angioedema. Int Arch Allergy Immunol. 2011;156:443-50 pubmed publisher
    ..Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease. ..
  10. Park K, Ryu E, Tosakulwong N, Wu Y, Edwards A. Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects. Mol Vis. 2009;15:200-7 pubmed
    ..No interaction with other AMD risk variants was observed. We were unable to replicate the reported association between SERPING1 and AMD in two independent groups of subjects. ..
  11. Martinez Saguer I, Rusicke E, Aygören Pürsün E, von Hentig N, Klingebiel T, Kreuz W. Pharmacokinetic analysis of human plasma-derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study. Transfusion. 2010;50:354-60 pubmed publisher
    ..5 hour for adults on IRT. pC1-INH concentrate has a long median terminal elimination half-life and rapidly reaches maximum plasma concentrations. This rapid onset of clinical efficacy is essential in patients suffering from HAE. ..
  12. Gösswein T, Kocot A, Emmert G, Kreuz W, Martinez Saguer I, Aygören Pürsün E, et al. Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet Genome Res. 2008;121:181-8 pubmed publisher
    ..It is, therefore, a valuable tool in prevention and adequate treatment of acute and life-threatening oedema. ..
  13. Farkas H, Szongoth M, Bely M, Varga L, Fekete B, Karadi I, et al. Angiooedema due to acquired deficiency of C1-esterase inhibitor associated with leucocytoclastic vasculitis. Acta Derm Venereol. 2001;81:298-300 pubmed
    ..Treatment with antimalarial agents resulted in complete resolution of symptoms and signs. Furthermore, C1-esterase inhibitor concentration and activity, as well as C1 levels, all returned to normal. ..
  14. Vitrat Hincky V, Gompel A, Dumestre perard C, Boccon Gibod I, Drouet C, Cesbron J, et al. Type III hereditary angio-oedema: clinical and biological features in a French cohort. Allergy. 2010;65:1331-6 pubmed publisher
    ..Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence. ..
  15. Caldwell E, Andreasen A, Blietz M, Serrahn J, VanderNoot V, Park Y, et al. Heparin binding and augmentation of C1 inhibitor activity. Arch Biochem Biophys. 1999;361:215-22 pubmed
    ..This is the first report of LMW heparin augmenting C1INH activity. Heparan sulfate neither interacted with C1INH nor did it augment C1INH activity. ..
  16. López Lera A, Garrido S, Roche O, Lopez Trascasa M. SERPING1 mutations in 59 families with hereditary angioedema. Mol Immunol. 2011;49:18-27 pubmed publisher
    ..An approach to the molecular effects associated to each of the mutations reported here was made when possible based on the available data of pathological variants of serpins. ..
  17. Kreuz W, Rusicke E, Martinez Saguer I, Aygören Pürsün E, Heller C, Klingebiel T. Home therapy with intravenous human C1-inhibitor in children and adolescents with hereditary angioedema. Transfusion. 2012;52:100-7 pubmed publisher
  18. Bork K, Staubach P, Eckardt A, Hardt J. Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency. Am J Gastroenterol. 2006;101:619-27 pubmed
    ..Our results add to the understanding of symptoms and course of HAE and may aid in the early recognition of an impending attack and improve clinical management. ..
  19. Ennis S, Jomary C, Mullins R, Cree A, Chen X, MacLeod A, et al. Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study. Lancet. 2008;372:1828-34 pubmed publisher
    ..SERPING1 encodes the C1 inhibitor, which has a crucial role in inhibition of complement component 1 (C1) and might implicate the classic pathway of complement activation in this disease. ..
  20. Farkas H, Jakab L, Temesszentandrási G, Visy B, Harmat G, Fust G, et al. Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol. 2007;120:941-7 pubmed
    ..Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis. ..
  21. Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119:267-74 pubmed
    ..The described swelling pattern is specific for HAE and allows a tentative diagnosis based on clinical symptoms and the course of the disease. ..
  22. Verpy E, Biasotto M, Brai M, Misiano G, Meo T, Tosi M. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. Am J Hum Genet. 1996;59:308-19 pubmed
    ..Moreover, it provides accurate positional information--and hence recognition of multiple substitutions, precise relationship with those already known, and often immediate identification of the nucleotide change. ..
  23. Lee A, Kulkarni M, Fang A, Edelstein S, Osborn M, Brantley M. The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. Br J Ophthalmol. 2010;94:915-7 pubmed publisher
    ..The hypothesis that SERPING1 has a modest effect on the risk of neovascular AMD is supported by our results. ..
  24. de Serres J, Gröner A, Lindner J. Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review. Transfus Apher Sci. 2003;29:247-54 pubmed
    ..There are numerous observational studies showing good efficacy and safety and a long post-marketing experience although few randomized placebo-controlled trials. ..
  25. Cicardi M, Bork K, Caballero T, Craig T, Li H, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67:147-57 pubmed publisher
    ..Here, we report the topics discussed during the meeting and evidence-based consensus about management approaches for HAE in adult/adolescent patients. ..
  26. McGlinchey P, McCluskey D. Hereditary angioedema precipitated by estrogen replacement therapy in a menopausal woman. Am J Med Sci. 2000;320:212-3 pubmed
    ..The pathophysiology of hereditary angioedema and its hormonal links are discussed. ..
  27. Kaplan A, Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:193-204 pubmed publisher
    ..Inhibition of bradykinin formation by novel agentscan provide targeted therapeutic approaches that address the pathophysiologic abnormalities. ..
  28. Mullins R, Faidley E, Daggett H, Jomary C, Lotery A, Stone E. Localization of complement 1 inhibitor (C1INH/SERPING1) in human eyes with age-related macular degeneration. Exp Eye Res. 2009;89:767-73 pubmed publisher
    ..These results indicate that C1INH protein is present in the retina and choroid, where it may regulate complement activation. ..
  29. Lu F, Zhao P, Fan Y, Tang S, Hu J, Liu X, et al. An association study of SERPING1 gene and age-related macular degeneration in a Han Chinese population. Mol Vis. 2010;16:1-6 pubmed
    ..We demonstrate that SNPs in SERPING1 are not significantly associated with AMD in the mainland Han Chinese population. ..
  30. Roche O, Blanch A, Caballero T, Sastre N, Callejo D, Lopez Trascasa M. Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain. Ann Allergy Asthma Immunol. 2005;94:498-503 pubmed
    ..The detected minimal prevalence of HAE in Spain is 1.09 per 100,000 inhabitants. Because this is a rare disease and some patients may be misdiagnosed, this prevalence could be higher. ..
  31. Bork K, Barnstedt S, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000;356:213-7 pubmed
    ..The formal genetics of this entity are suggestive of an X-linked dominant mode of inheritance. For this disorder we propose the term hereditary angioedema type 3 (HAE III). ..
  32. Kalmar L, Hegedus T, Farkas H, Nagy M, Tordai A. HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor gene. Hum Mutat. 2005;25:1-5 pubmed
    ..This database may facilitate future comprehensive analyses of C1-INH mutations and also provide regular help for molecular diagnostic testing of HAE patients in different centers. ..
  33. Davis A, Mejia P, Lu F. Biological activities of C1 inhibitor. Mol Immunol. 2008;45:4057-63 pubmed publisher
  34. Cai S, Davis A. Complement regulatory protein C1 inhibitor binds to selectins and interferes with endothelial-leukocyte adhesion. J Immunol. 2003;171:4786-91 pubmed
    ..It may also provide another example of the multifaceted anti-inflammatory effects of C1INH in various animal models and human diseases. ..
  35. Patston P, Schapira M. Regulation of C1-inhibitor function by binding to type IV collagen and heparin. Biochem Biophys Res Commun. 1997;230:597-601 pubmed
    ..At low ionic strength the stoichiometry increased to 2.55. These data provide the first report that C1-inhibitor can bind to type IV collagen and also show that C 1-inhibitor can be regulated by ligand binding. ..
  36. Johnston D. Diagnosis and management of hereditary angioedema. J Am Osteopath Assoc. 2011;111:28-36 pubmed
    ..The author presents two hypothetical cases of HAE and reviews the clinical hallmarks of this condition, diagnostic tests, and available treatments. ..
  37. Farkas H, Harmat G, Fust G, Varga L, Visy B. Clinical management of hereditary angio-oedema in children. Pediatr Allergy Immunol. 2002;13:153-61 pubmed
    ..Undesirable adverse effects can be avoided and the patient's quality of life enhanced considerably by administering the lowest effective drug dose. ..
  38. Bork K, Hardt J, Schicketanz K, Ressel N. Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med. 2003;163:1229-35 pubmed
    ..To prevent a fatal outcome, it is essential to instruct patients and their relatives about the first signs of laryngeal edemas and the necessary procedures to follow. ..
  39. Speletas M, Boukas K, Papadopoulou Alataki E, Tsitsami E, Germenis A. Hereditary angioedema in Greek families caused by novel and recurrent mutations. Hum Immunol. 2009;70:925-9 pubmed publisher
    ..Our study identified a novel mutagenesis mechanism for HAE pathogenesis, providing additional evidence for the genetic heterogeneity of the disease. ..
  40. Caballero T, Farkas H, Bouillet L, Bowen T, Gompel A, Fagerberg C, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012;129:308-20 pubmed publisher
    ..A consensus for the management of female patients with HAE-C1-INH is presented. ..
  41. Kessel A, Peri R, Perricone R, Guarino M, Vadasz Z, Novak R, et al. The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency. Clin Exp Immunol. 2012;167:422-8 pubmed publisher
    ..HAE patients have enhanced production of autoantibodies due most probably to the increased activation of B cells, which was found to be in association with a high expression of TLR-9. ..
  42. Lathem W, Grys T, Witowski S, Torres A, Kaper J, Tarr P, et al. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Mol Microbiol. 2002;45:277-88 pubmed
    ..Cleavage of C1-INH by StcE could plausibly cause localized pro-inflammatory and coagulation responses resulting in tissue damage, intestinal oedema and thrombotic abnormalities. ..
  43. Freiberger T, Kolarova L, Mejstrik P, Vyskocilova M, Kuklinek P, Litzman J. Five novel mutations in the C1 inhibitor gene (C1NH) leading to a premature stop codon in patients with type I hereditary angioedema. Hum Mutat. 2002;19:461 pubmed
    ..Moreover, two previously described mutations in the reactive center of C1 inh, p.R444C and p.R444H, have been detected in four unrelated patients with type II HAE. ..
  44. Lathem W, Bergsbaken T, Witowski S, Perna N, Welch R. Acquisition of stcE, a C1 esterase inhibitor-specific metalloprotease, during the evolution of Escherichia coli O157:H7. J Infect Dis. 2003;187:1907-14 pubmed
    ..coli 1 complex in a stepwise manner. These data refine the sequential model of E. coli O157:H7 evolution proposed elsewhere. ..
  45. Davis A. The pathogenesis of hereditary angioedema. Transfus Apher Sci. 2003;29:195-203 pubmed
  46. Kalmar L, Bors A, Farkas H, Vas S, Fandl B, Varga L, et al. Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema. Hum Mutat. 2003;22:498 pubmed
    ..14107delA, g.16749_;16775dup, g.16810T>A, g.16885C>G) were detected in 16 families affecting primarily exon 3 (6/13) of the C1INH gene. In the 3 remaining families, known mutations were identified affecting primarily exon 8 (2/3). ..
  47. Moreau M, Garbacki N, Molinaro G, Brown N, Marceau F, Adam A. The kallikrein-kinin system: current and future pharmacological targets. J Pharmacol Sci. 2005;99:6-38 pubmed
  48. Skriver K, Radziejewska E, Silbermann J, Donaldson V, Bock S. CpG mutations in the reactive site of human C1 inhibitor. J Biol Chem. 1989;264:3066-71 pubmed
  49. Carter P, Duponchel C, Tosi M, Fothergill J. Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements. Eur J Biochem. 1991;197:301-8 pubmed
    ..There is no obvious promoter site of the TATA-box type at the 5' end of the gene, but instead it contains a region of potential H-DNA structure similar to that found upstream of the human c-myc gene. ..
  50. Akuffo E, Davis J, Fox S, Gloger I, Hosford D, Kinsey E, et al. The discovery and early validation of novel plasma biomarkers in mild-to-moderate Alzheimer's disease patients responding to treatment with rosiglitazone. Biomarkers. 2008;13:618-36 pubmed
    ..These results are discussed in light of the pathology and other recently published data. ..
  51. Hemels M, Geelen S, Hoekstra M, Meijer Y. [Episodes of angioedema in children with C1 esterase inhibitor deficiency]. Ned Tijdschr Geneeskd. 2006;150:631-4 pubmed
    ..In patients who have more than one episode of severe angioedema per month, daily treatment with tranexamic acid should be considered. Both of these patients were not receiving daily treatment. ..
  52. Windfuhr J, Alsenz J, Loos M. The critical concentration of C1-esterase inhibitor (C1-INH) in human serum preventing auto-activation of the first component of complement (C1). Mol Immunol. 2005;42:657-63 pubmed
    ..Addition of highly purified C1-INH or NHS as source of C1-INH to C1-INH-depleted serum to a final concentration of 55 microg/ml (22% of normal C1-INH concentration in HS) was sufficient to control spontaneous C1-activation. ..
  53. Lener M, Fernandes M, Poirier C, Bazzali Hernandez C, Tosi M, Meo T. The C1 inhibitor encoding gene (C1nh) maps to mouse chromosome 2. Mamm Genome. 1998;9:94 pubmed