Other names: C1 Esterase Inhibitor, Functional, C1 Est.Inhib.Funct., Hereditary Angioedema (HAE)
Optimal Result:
67 - 100 %.
C1 inhibitor is a multispecific, protease inhibitor that is present in normal human plasma and serum, and which regulates enzymes of the complement, coagulation, fibrinolytic, and kinin-forming systems. The enzymes (proteases) regulated by this protein include the C1r and C1s subunits of the activated first component of complement, activated XIIa, kallikrein (Fletcher factor), and plasmin.
In addition to decreased C1 esterase inhibitor in the serum of patients with hereditary angioneurotic edema, a unique polypeptide kinin is increased in plasma from C1 esterase inhibitor deficient patient during attacks of swelling. Danazol, a synthetic androgenic inhibitor of gonadotropin release, with little virilizing potential, decreases the number of clinical attacks in cases of hereditary angioneurotic edema. Patients with attacks of hereditary angioneurotic edema also have low total complement, C4 and C2. Consequently, measurement of serum C4 is an often used test. Hereditary angioneurotic edema is transmitted as an autosomal dominant trait. Heterozygotes also show decreased levels of C1 esterase inhibitor. During acute attacks of the disease, complement factors C4 and C2 can be markedly reduced, but C1 and C3 are normal. The initiating stimulus of clinical attacks is often unknown.
Angioedema may also be an acquired illness. The acquired form includes nonhereditary C1 esterase deficiency; drug induced, allergic, and idiopathic forms, angioedema associated with autoimmune disease, especially with systemic lupus erythematosus and hypereosinophilia; angioedema occasionally associated with malignancy; and angioedema caused by physical stimuli. Angioedema has occasionally been known to precede development of lymphoproliferative disorders.
What is the difference between the C1 Inhibitor, Protein test and the C1 Inhibitor, Functional test?
The C1 Inhibitor, Protein test measures the concentration of the C1 esterase inhibitor protein using a fixed rate time nephelometry method. The C1 Inhibitor, Functional test measures the relative functionality of an individual’s C1 esterase inhibitor protein using an enzyme immunoassay.
Both tests may be helpful in the diagnosis of hereditary angioedema (HAE). HAE is an autosomal dominant genetic disorder that manifests in 3 ways:
- Type I is the most common type of HAE, affecting about 85% of patients.1 It is caused by mutations in the SERPING1 gene and is characterized by low levels (<11 ng/mL) of the protein and normal (>68%) protein function.
- Type II affects about 15% of HAE patients1 and is also caused by SERPING1 mutations. Concentrations of the C1 inhibitor protein are normal (11-26 ng/mL), but the protein is dysfunctional (functional activity <40%).
- Type III is a rare type of HAE2 that is associated with mutations in the F12 gene, which encodes the coagulation protein factor XII. HAE type III symptoms are exacerbated by pregnancy and oral contraceptives. The C1 esterase inhibitor protein concentration is typically normal, as is the protein function.
The C1 esterase inhibitor (C1-INH) concentration assay can be used to distinguish type I hereditary angioedema (HAE), with low C1-INH concentration, from type II HAE characterized by normal or elevated concentration. Furthermore, serum C1q concentrations can be used to differentiate HAE from acquired angioedema (AAE) forms of angioedema as the latter is characterized by decreased C1q antigen concentration and autoantibodies against C1-INH. Genetic analysis for SERPING1 variants status may also help exclude HAE.
-Nonfunctional C1-INH results are consistent with HAE
-Patients with current attacks may also have low C2 and C4 concentrations due to C1 activation and complement activation of the classical pathway (consumption).
-Patients with acquired C1-INH deficiency have a low C1q concentration and/or function in addition to low C1-INH.
Laboratory Features Consistent with Hereditary and Acquired Angioedema Subtypes
|
|
Type I hereditary angioedema |
Type II hereditary angioedema |
Acquired angioedema |
|
C1 esterase inhibitor (C1-INH) concentration |
Low |
Normal/high |
Low |
|
C1-INH function |
Low |
Low |
Low/normal |
|
C4 concentration |
Low |
Low |
Low |
|
C1q concentration |
Normal |
Normal |
Low |
|
Anti-C1-INH antibodies |
Absent |
Absent |
Present |
|
C3 concentration |
Normal |
Normal |
Normal |
|
Family history |
Yes |
Yes |
No |
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C1 esterase inhibitor is decreased in hereditary angioneurotic edema; decrease may be functional or quantitative.
A deficiency of functionally active C1-INH may lead to life-threatening angioedema. Two major forms of C1-INH deficiency have been reported: the congenital form, termed hereditary angioedema (HAE), and the acquired form that is associated with a variety of diseases, including lymphoid malignancies. HAE is characterized by transient but recurrent attacks of nonpruritic swelling of various tissues throughout the body. The symptomatology depends upon the organs involved. Intestinal attacks lead to a diversity of symptoms including pain, cramps, vomiting, and diarrhea. The most frequent cause of death in this disease is airway obstruction secondary to laryngeal edema occurring during an attack. There are 2 types of HAE that can be distinguished biochemically. Patients with the more common type (85% of HAE patients) have low levels of functional C1-INH and C1-INH antigen. Patients with the second form (15% of HAE patients) have low levels of functional C1-INH but normal or increased levels of C1-INH antigen that is dysfunctional. The variable nature of the symptoms at different time periods during the course of the disease makes it difficult to make a definitive diagnosis based solely on clinical observation.
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Our user-friendly form guides you through a quick, simple submission process, making it easy to enter your health metrics.
Add your results anytime with our easy entry form. It's quick, guided, and helps you stay organized — free for all members.
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After collecting lab results from different providers, you can download your entire history combined into a single file.
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Our inclusive service handles the data entry for your lab reports. Just submit your information and we'll take care of the rest. Complete plan members receive one report entered for free, then $15 per report after that. Unlimited plan members receive ten report entries for free, then $15 per report after that.
Our inclusive service handles the data entry for your lab reports. Just submit your information and we'll take care of the rest.
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Our data entry forms offer an easy, fast, and free way for you to input the reports yourself. Self-entry allows you to add an unlimited number of reports at no cost. We make the self-entry process user-friendly, providing dozens of templates that pre-populate the most popular laboratory panels and offering instant feedback on entered values.
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Yes, you can. When entering values for the biomarker, you will see an "Edit Range" button. Click this button, and you'll have the option to enter a custom range.
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