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 |
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.
Understand and improve your laboratory results with our health dashboard.
Upload your lab reports and get your interpretation today.
Our technology helps to understand, combine, track, organize, and act on your medical lab test results.
Interpret Your Lab Results
Upload your lab report, and we'll interpret and provide you with recommendations today.
Get StartedMonthly plan
Annual plan
Own it for life
Our exclusive data entry service is a convenient way to get your results into your private dashboard. Simply attach an image or a file of your lab test results, and one of our qualified data entry team members will add the results for you. We support all sorts of files, whether PDFs, JPGs, or Excel. This service is excellent whether you have a lot of reports to upload or are too busy to do the data entry yourself.
We strive to make the data entry process easy for you. Whether by offering dozens of templates to choose from that pre-populate the most popular laboratory panels or by giving you instant feedback on the entered values. Our data entry forms are an easy, fast, and convenient way to enter the reports yourself. There is no limit on how many lab reports you can upload.
$15 /month
billed every month
Most popular
Data entry included
$79 /year
$6.60/month billed annually
Data entry included
$250 /once
own it for life
Are You a Health Professional?
Get started with our professional plan
Welcome to Healthmatters Pro.
Save time on interpreting lab results with the largest database of biomarkers online. In-depth research on any test at your fingertips, all stored and tracked in one place. Learn more
Pro Monthly Plus
for health professionals
$75 per month
At HealthMatters, we're committed to maintaining the security and confidentiality of your personal information. We've put industry-leading security standards in place to help protect against the loss, misuse, or alteration of the information under our control. We use procedural, physical, and electronic security methods designed to prevent unauthorized people from getting access to this information. Our internal code of conduct adds additional privacy protection. All data is backed up multiple times a day and encrypted using SSL certificates. See our Privacy Policy for more details.
14.3.3 ETA PROTEIN, Acetylcholine Receptor (AChR) Antibody, Activated partial thromboplastin time (APTT), Alpha 2-Macroglobulins, Qn, ANA SCREEN A, ANA SCREEN B, ANA SCREEN, IFA, ANA titer, Anti-C1Q Ab, IgG (RDL), Anti-DBL-Strand DNA Ab, Anti-dsDNA (Double-stranded) Ab by Farr method (RDL), Anti-Smith Antibody, Anticardiolipin Ab, IgM, Anticardiolipin Ab,IgA,Qn, Anticardiolipin Ab,IgG,Qn, Antinuclear Antibodies (ANA) Screen, Reflex ANA IFA dsDNA Antibodies, Antinuclear Antibodies Direct (ANA Direct), Antiphosphatidylserine IgA, Antiphosphatidylserine IgG, Antiphosphatidylserine IgM, Baski sleepy, C1 Esterase Inhibitor, Func, C1 Esterase Inhibitor, Serum, C3A Desarg Fragment, CARDIOLIPIN AB (IGA), CARDIOLIPIN AB (IGG), CARDIOLIPIN AB (IGM), Carnitine, Free, Carnitine, Total, CCP Antibodies IgG/IgA, Centromere, Chromatin, Coccidioides Ab by CF, Coccidioides Ab, IgG, EIA, Coccidioides Ab, IgM, EIA, Complement C3, Complement C3a, Complement C4, Serum, Complement C4a, Complement, Total (CH50), Complement, Total (CH50) / Quest, Cyclic Citrullinated Peptide Antibody, Dilute Russell's viper venom time (dRVVT), Diphtheria Antitoxoid Antibody, DNA AB Double Stranded Titer, DNA Double-Stranded Ab, IgG, DRVVT SCREEN, ds-DNA Antibody, IgG, dsDNA, Erythrocyte Sedimentation Rate (ESR), F004-IgE Wheat, Free Kappa Lt Chains, Serum, Free Lambda Lt Chains, Serum, Gastrin, Histamine, Plasma, Histone, HLA-B27 (Human Leukocyte Antigen B27), Immature Grans (Abs), Immature Granulocytes (%), Immunofixation Result, Serum, Immunoglobulin A, Qn, Serum, Immunoglobulin D, Quant, Serum, Immunoglobulin E, Total, Immunoglobulin G, Qn, Serum, Immunoglobulin M, Qn, Serum, Interleukin-2, Serum, Interleukin-6, Jo 1 Antibodies, IgG, Serum, JO-1, Kappa/Lambda Ratio, Serum, Liver-Kidney Microsomal Antibodies, Lupus Anticoagulant, Measles Antibodies, IgG, Mumps Abs, IgG, PHOSPHATIDYLETHANOLAMINE AB (IGA), PHOSPHATIDYLETHANOLAMINE AB (IGG), PHOSPHATIDYLETHANOLAMINE AB (IGM), PHOSPHATIDYLSERINE AB (IGA), PHOSPHATIDYLSERINE AB (IGG), PHOSPHATIDYLSERINE AB (IGM), Plasminogen Activator Inhibitor (PAI-1) AG, Prothrombin Fragment 1.2, Prothrombin Time (PT), Prothrombin Time (PT) INR, RA Latex Turbid, Reptilase Clotting Time, RF, IgA by EIA (RDL), RF, IgG by EIA (RDL), RF, IgM by EIA (RDL), Rheumatoid factor (RF), RNP/Sm, Scl-70, Sm, SM/RNP Antibody, SSA, SSB, ssDNA, Tetanus Antitoxoid IgG Ab, TGF-b1, Thrombin time, Thrombin-Antithrombin TAT, Transforming Growth Factor beta, Plasma, Tryptase, Varicella-Zoster Virus (VZV) DNA, Qualitative, Real-Time PCR, VEGF, Plasma, Von Willebrand Factor Antigen (vWF), vWF Activity