Test Catalog

Test Id : C1INF

C1 Esterase Inhibitor, Functional, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosing hereditary angioedema

 

Monitoring response to C1 esterase inhibitor replacement therapy

Method Name
A short description of the method used to perform the test

Enzyme Immunoassay (EIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

C1 Esterase Inhib, Functional, S

Aliases
Lists additional common names for a test, as an aid in searching

C1 Esterase Inh,Func (QN)

Functional C'1 Esterase

Hereditary Angioedema Panel (3 tests)

Hereditary Angioedema, HAE

Specimen Type
Describes the specimen type validated for testing

Serum Red

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Fasting, preferred but not required

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Immediately after specimen collection, place the tube on wet ice.

2. Centrifuge at 4 degrees C and aliquot serum into a 5-mL plastic vial.

3. Freeze specimen within 30 minutes.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.4 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

DRY ICE REGULAR HOURS: Centrifuge at 4 degrees C, aliquot, transport on dry ice
OFF HOURS: Centrifuge at 4 degrees C, aliquot, freeze within 30 minutes. Transport next working day on dry ice.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Red Frozen (preferred) 28 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosing hereditary angioedema

 

Monitoring response to C1 esterase inhibitor replacement therapy

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

C1 esterase inhibitor (C1-INH) is a multispecific protease inhibitor that is present in normal human plasma and serum and 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 (the C1qrs complex), activated Hageman factor (factor XIa), kallikrein (Fletcher factor), and plasmin.

 

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, which is associated with a variety of diseases, acquired angioedema (AAE).

 

In HAE, there is insufficient C1-INH to negatively regulate bradykinin release and stop angioedema attacks from occurring. The mechanism of HAE attacks is distinct from an allergic angioedema as it is not mediated by histamine release via mast cell activation. Therefore, HAE patients are unresponsive to antihistamines or corticosteroids.

There are 2 main types of HAE that are attributed to C1-INH deficiency (Type I) or dysfunction (Type II), resulting in C1-INH activity ranging from less than 20% to 50% of normal. Type I HAEs, representing approximately 85% of patients, are associated with low circulating concentrations of C1-INH, leading to a concomitant decrease in C1-INH function. In Type II HAEs, normal or elevated concentrations of functionally inactive C1-INH are produced. The relative proportion of Type I and Type II HAE may differ based on geographical location.

 

A third HAE subtype with unknown prevalence termed "HAE with normal C1-INH" has been described. Although poorly characterized, a minority of these patients is known to harbor a variant in Factor XII; the disease origin for the remainder of patients remains unknown. Factor XII is the zymogen form of Factor XIIa and plays a key role in bradykinin production as part of the contact system.

 

Angioedema due to C1-INH deficiency can also be acquired during adulthood in the fifth decade of life or later. The prevalence of AAE is extremely low and is estimated at 10% of HAE. AAE is frequently associated with monoclonal gammopathies or lymphoproliferative disease as well as different types of cancer and autoimmune diseases. AAE may be caused by development of anti-C1-INH autoantibodies, which act to reduce the functional activity or increase the catabolism of C1-INH.

 

For patients exhibiting symptoms associated with HAE, evaluation of pertinent family history in combination with laboratory results for C1-INH function and concentration, C4 concentration, and C1q concentration can assist in HAE diagnosis and determination of HAE type. Identification of low C1-INH function and low C4 concentration support the diagnosis of HAE and was found to have 98% specificity towards C1-INH deficiency and a negative predictive value of 95%. C4 is decreased owing to excessive consumption through the classical pathway in the absence of inhibition by C1-INH. Due to low disease prevalence, false-positive results are common and therefore, repeated testing is recommended to confirm findings.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

>67% normal (normal)

41-67% normal (equivocal)

<41% normal (abnormal)

Interpretation
Provides information to assist in interpretation of the test results

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.

 

Table. 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

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay is a functional test and is dependent on correct sampling, storage, and shipping conditions.

 

Absent (or low) C1 esterase inhibitor function should be confirmed with a new serum specimen to confirm that inactivation has not occurred during shipping.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Stoppa-Lyonnet D, Tosi M, Laurent J, Sobel A, Lagrue G, Meo T: Altered C1 inhibitor genes in type I hereditary angioedema. N Engl J Med. 1987 Jul;317(1):1-6. doi: 10.1056/NEJM198707023170101

2. Frigas E: Angioedema with acquired deficiency of the C1 inhibitor: a constellation of syndromes. Mayo Clin Proc. 1989 Oct;64(10):1269-1275. doi: 10.1016/s0025-6196(12)61290-7

3. Frazer-Abel A, Sepiashvili L, Mbughuni MM, Willrich MA: Overview of laboratory testing and clinical presentations of complement deficiencies and dysregulation. Adv Clin Chem. 2016;77:1-75. doi: 10.1016/bs.acc.2016.06.001

Method Description
Describes how the test is performed and provides a method-specific reference

The Quidel C1 inhibitor enzyme immunoassay for the quantitation of functional C1 inhibitor protein in human serum or plasma is a four-step procedure. In the first step, standards, controls, and test specimens are incubated with C1 esterase inhibitor (C1-INH) reactant (biotinylated, activated C1s). During this incubation, functionally active C1-INH present in the standards, controls, and test samples will bind to the biotinylated C1-INH reactant to form complexes. In the second step, an aliquot of the incubation mixtures containing biotinylated C1-INH reactant is added to microtiter wells pre-coated with avidin. C1-INH reactant: C1-INH complexes present in the standards, controls, or specimens will bind to the avidin-coated microassay wells. After incubation, a wash cycle removes unbound material. In the third step, horseradish peroxidase (HRP)-conjugated goat anti-C1-INH is added to each test well. During this step, the HRP-conjugated anti-C1-INH binds to the C1-INH reactant: C1-INH complexes, which were captured on the surface of the avidin-coated microassay wells. After incubation, a wash cycle removes excess conjugate. In the fourth step, a chromogenic enzyme substrate is added to each microassay well. The bound HRP-conjugate reacts with the substrate forming a blue color. After incubation, the enzyme reaction is stopped chemically, forming a yellow color and the color intensity is measured spectrophotometrically at 450 nm. The color intensity of the reaction mixture is proportional to the concentration of functional C1-INH protein present in the test specimens, standards, and controls.(Package insert: C1-Inhibitor Enzyme Immunoassay, Quidel; 09/2021)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83520

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
C1INF C1 Esterase Inhib, Functional, S 48494-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
C1INF C1 Esterase Inhib, Functional, S 48494-9

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports