Research progress of complement 1 esterase inhibitor in the treatment of hereditary angioedema_West China Medical Journal

Authors：

SUN Qin ¹ , ZHANG Haihong ¹ , GONG Li ² ,  WAN Zhi ¹

1. Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Outpatient Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WAN Zhi, Email: wanzhi4115@wchscu.cn

Keywords：

Complement 1 esterase inhibitor; hereditary angioedema; treatment

DOI：

10.7507/1002-0179.202403285

Video：

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Abstract Full text Figures/Tables Video References Cited by

Complement 1 esterase inhibitor (C1-INH) is a serine protease inhibitor, which is an important regulatory substance in the plasma cascade reaction and can regulate the complement system and bradykinin-forming system. hereditary angioedema (HAE) is a rare autosomal dominant inherited disease, mainly caused by a mutation of the gene controlling the synthesis of C1-INH resulting in reduced or dysfunctional levels of C1-INH in patients. C1-INH substitution therapy is one of the main therapeutic strategies for controlling HAE attacks. This article mainly collates and analyzes related research literature, summarizes the progress of C1-INH treatment of HAE, and provides some references for clinicians to treat HAE.

Citation： SUN Qin, ZHANG Haihong, GONG Li, WAN Zhi. Research progress of complement 1 esterase inhibitor in the treatment of hereditary angioedema. West China Medical Journal, 2025, 40(1): 106-112. doi: 10.7507/1002-0179.202403285 Copy

1.	Sinnathamby ES, Issa PP, Roberts L, et al. Hereditary angioedema: diagnosis, clinical implications, and pathophysiology. Adv Ther, 2023, 40(3): 814-827.
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3.	Verpy E, Biasotto M, Brai M, et al. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. Am J Hum Genet, 1996, 59(2): 308-319.
4.	Zuraw BL, Herschbach J. Detection of C1 inhibitor mutations in patients with hereditary angioedema. J Allergy Clin Immunol, 2000, 105(3): 541-546.
5.	Bork K, Barnstedt SE, Koch P, et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet, 2000, 356(9225): 213-217.
6.	Dewald G, Bork K. Missense mutations in the coagulation factor Ⅻ (hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun, 2006, 343(4): 1286-1289.
7.	Bork K, Machnig T, Wulff K, et al. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence. Orphanet J Rare Dis, 2020, 15(1): 289.
8.	Rosen FS, Pensky J, Donaldson V, et al. Hereditary angioneurotic edema: two genetic variants. Science, 1965, 148(3672): 957-958.
9.	Bork K, Meng G, Staubach P, et al. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med, 2006, 119(3): 267-274.
10.	Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc, 2000, 75(4): 349-354.
11.	Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol, 2012, 130(3): 692-697.
12.	Cicardi M, Zuraw BL. Angioedema due to bradykinin dysregulation. J Allergy Clin Immunol Pract, 2018, 6(4): 1132-1141.
13.	Gadek JE, Hosea SW, Gelfand JA, et al. Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor. N Engl J Med, 1980, 302(10): 542-546.
14.	Frank MM. Recombinant and plasma-purified human C1 inhibitor for the treatment of hereditary angioedema. World Allergy Organ J, 2010, 3(9 Suppl): S29-S33.
15.	Donaldson VH, Evans RR. A biochemical abnormality in herediatry angioneurotic edema: absence of serum inhibitor of C'1-esterase. Am J Med, 1963, 35: 37-44.
16.	Silverman GA, Bird PI, Carrell RW, et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem, 2001, 276(36): 33293-33296.
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18.	Joseph K, Kaplan AP. Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol, 2005, 86: 159-208.
19.	Bas M, Adams V, Suvorava T, et al. Nonallergic angioedema: role of bradykinin. Allergy, 2007, 62(8): 842-856.
20.	Joseph K, Tuscano TB, Kaplan AP. Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma. Ann Allergy Asthma Immunol, 2008, 101(3): 279-286.
21.	Joseph K, Tholanikunnel BG, Kaplan AP. Factor Ⅻ-independent cleavage of high-molecular-weight kininogen by prekallikrein and inhibition by C1 inhibitor. J Allergy Clin Immunol, 2009, 124(1): 143-149.
22.	Joseph K, Tholanikunnel TE, Kaplan AP. Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. Ann Allergy Asthma Immunol, 2010, 104(1): 50-54.
23.	Dobó J, Major B, Kékesi KA, et al. Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP)-1. PLoS One, 2011, 6(5): e20036.
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1. Sinnathamby ES, Issa PP, Roberts L, et al. Hereditary angioedema: diagnosis, clinical implications, and pathophysiology. Adv Ther, 2023, 40(3): 814-827.
2. Pappalardo E, Cicardi M, Duponchel C, et al. Frequent de novo mutations and exon deletions in the C1inhibitor gene of patients with angioedema. J Allergy Clin Immunol, 2000, 106(6): 1147-1154.
3. Verpy E, Biasotto M, Brai M, et al. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. Am J Hum Genet, 1996, 59(2): 308-319.
4. Zuraw BL, Herschbach J. Detection of C1 inhibitor mutations in patients with hereditary angioedema. J Allergy Clin Immunol, 2000, 105(3): 541-546.
5. Bork K, Barnstedt SE, Koch P, et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet, 2000, 356(9225): 213-217.
6. Dewald G, Bork K. Missense mutations in the coagulation factor Ⅻ (hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun, 2006, 343(4): 1286-1289.
7. Bork K, Machnig T, Wulff K, et al. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence. Orphanet J Rare Dis, 2020, 15(1): 289.
8. Rosen FS, Pensky J, Donaldson V, et al. Hereditary angioneurotic edema: two genetic variants. Science, 1965, 148(3672): 957-958.
9. Bork K, Meng G, Staubach P, et al. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med, 2006, 119(3): 267-274.
10. Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc, 2000, 75(4): 349-354.
11. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol, 2012, 130(3): 692-697.
12. Cicardi M, Zuraw BL. Angioedema due to bradykinin dysregulation. J Allergy Clin Immunol Pract, 2018, 6(4): 1132-1141.
13. Gadek JE, Hosea SW, Gelfand JA, et al. Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor. N Engl J Med, 1980, 302(10): 542-546.
14. Frank MM. Recombinant and plasma-purified human C1 inhibitor for the treatment of hereditary angioedema. World Allergy Organ J, 2010, 3(9 Suppl): S29-S33.
15. Donaldson VH, Evans RR. A biochemical abnormality in herediatry angioneurotic edema: absence of serum inhibitor of C'1-esterase. Am J Med, 1963, 35: 37-44.
16. Silverman GA, Bird PI, Carrell RW, et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem, 2001, 276(36): 33293-33296.
17. Davis AE 3rd. The pathophysiology of hereditary angioedema. Clin Immunol, 2005, 114(1): 3-9.
18. Joseph K, Kaplan AP. Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol, 2005, 86: 159-208.
19. Bas M, Adams V, Suvorava T, et al. Nonallergic angioedema: role of bradykinin. Allergy, 2007, 62(8): 842-856.
20. Joseph K, Tuscano TB, Kaplan AP. Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma. Ann Allergy Asthma Immunol, 2008, 101(3): 279-286.
21. Joseph K, Tholanikunnel BG, Kaplan AP. Factor Ⅻ-independent cleavage of high-molecular-weight kininogen by prekallikrein and inhibition by C1 inhibitor. J Allergy Clin Immunol, 2009, 124(1): 143-149.
22. Joseph K, Tholanikunnel TE, Kaplan AP. Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. Ann Allergy Asthma Immunol, 2010, 104(1): 50-54.
23. Dobó J, Major B, Kékesi KA, et al. Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP)-1. PLoS One, 2011, 6(5): e20036.
24. Csuka D, Veszeli N, Varga L, et al. The role of the complement system in hereditary angioedema. Mol Immunol, 2017, 89: 59-68.
25. Schapira M, Scott CF, Colman RW. Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest, 1982, 69(2): 462-468.
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West China Medical Journal

Research progress of complement 1 esterase inhibitor in the treatment of hereditary angioedema

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