C1 esterase inhibitor
| Plasma protease C1 inhibitor | ||
|---|---|---|
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| other names |
C1 esterase inhibitor, C1-inhibiting factor, Serpin G1 |
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| Properties of human protein | ||
| Mass / length primary structure | 500 amino acids , 55,154 Da | |
| Identifier | ||
| Gene name | SERPING1 | |
| External IDs | ||
| Drug information | ||
| ATC code | B02 AB03 | |
| Inhibitor classification | ||
| MEROPS | I04.024 | |
| Orthologue (human) | ||
| Entrez | 710 | |
| Ensemble | ENSG00000149131 | |
| UniProt | P05155 | |
| Refseq (mRNA) | NM_000062.2 | |
| Refseq (protein) | NP_000053.2 | |
| PubMed search |
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The C1 esterase inhibitor (C1-INH, C1 inhibitor) is a serine protease inhibitor belonging to the serpins that controls the activation of the complement factor C1 and thus regulates the complement system . The normal value in the blood is around 0.25-0.45 g / l.
description
C1-INH is the largest member of the Serpin class of proteins. It is probably the most highly glycosylated protein. Notably, it has O-glycosylated residues which are unusual for non-membrane bound proteins (the immunoglobulins IgA1 and IgD are other examples).
genetics
The human C1 esterase inhibitor gene is located on the eleventh chromosome (11q11-q13.1).
Diseases
A deficiency in C1 esterase inhibitor is known as hereditary angioedema (outdated: hereditary angioneurotic edema). It usually presents with recurring swellings ( edema ) of the skin, mucous membranes and internal organs, which under certain circumstances can be life-threatening. It is estimated that around one in 10,000 to 50,000 people is affected, but the number of unreported cases is probably much higher. In 85% of the cases the level of C1-INH is lowered, while in 15% the protein is circulating in normal amounts but is not functional.
Therapeutic use
Hereditary angioedema
In patients with hereditary angioedema and frequent seizures, human C1-INH is given for treatment and prophylaxis. It can also reduce the duration or severity of the seizures.
Potential areas of application
Activation of the complement system can cause damage to cells. Inhibition of the complement system may therefore be of therapeutic benefit, for example after a heart attack to the harmful consequences of by the lack of oxygen caused necrosis of heart muscle cells to prevent: Under Continuous cardiac muscle cells spill their contents into the extracellular environment and thus activate the complement system, which phagocytes attracted which produce peroxidase and other toxic activators. These have a harmful effect on the surviving heart muscle cells. The inhibition of the complement system could counteract this.
In addition, C1 esterase inhibitors could become an option for the treatment of vascular leak syndrome , a side effect of interleukin-2 therapy.
It is also being investigated whether treatment with recombinant C1 esterase inhibitor can suppress the rejection reaction after kidney transplantation .
Finished medicinal products
Human C1 esterase inhibitor for therapeutic use is obtained from human blood plasma or produced in the milk of transgenic rabbits using recombinant DNA technology (rhC1-INH, conestat alfa ).
Trade names:
Individual evidence
- ↑ Caliezi C, Wuillemin WA, Zeerleder S, Redondo M, Eisele B, CE Hack: C1-esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema . In: Pharmacol Rev , 2000, 52, pp. 91-112.
- ↑ CE Hack, AC Ogilvie, B Eisele, PM Jansen, J Wagstaff, LG Thijs: Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. . In: Prog Clin Biol Res . 388, 1994. PMID 7831367 .
- ↑ Xavier Tillou, et al .: Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons . In: Kidney International . 78, No. 2, July 2010, pp. 152-159. doi : 10.1038 / ki.2010.75 . PMID 20336054 . (Fig.)
