Test Catalog

Test Id : C4FX

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C4 Complement, Functional, Serum

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Overview

Test Catalog

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

Diagnosis of C4 deficiency

 

Investigation of a patient with an undetectable total complement level

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

Automated Liposome Lysis Assay

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

C4 Complement, Functional, S

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

C4

Complement

Fourth Component of Complement

Functional C4

Functional Complement

Hemolytic C4

Hemolytic Complement

Specimen Type
Describes the specimen type validated for testing

Serum Red

Ordering Guidance

The total complement assay (COM / Complement, Total, Serum) should be used as a screen for suspected complement deficiencies before ordering individual complement component assays. A deficiency of an individual component of the complement cascade will result in an undetectable total complement level.

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

Patient Preparation: Fasting preferred

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Collection Container/Tube: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

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

2. Centrifuge and aliquot serum into plastic vial.

3. Immediately freeze specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

0.5 mL

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

Gross hemolysis OK
Gross lipemia Reject
Gross icterus OK

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 14 days

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

Diagnosis of C4 deficiency

 

Investigation of a patient with an undetectable total complement level

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

Complement proteins are components of the innate immune system. There are 3 pathways to complement activation: 1) the classical pathway, 2) the alternative (or properdin) pathway, and 3) the lectin (or mannan-binding lectin) pathway. The classical pathway of the complement system is composed of a series of proteins that are activated in response to the presence of immune complexes. A single IgM molecule or 2 IgG molecules are sufficient to trigger activation of the recognition complex initiated by C1q. The activation process triggers a cascade that includes an amplification loop. The amplification loop is mediated by C3, with cleavage of a series of proteins, and results in 3 main end products: 1) anaphylatoxins that promote inflammation (C3a, C5a), 2) opsonization peptides that are chemotactic for neutrophils (C3b) and facilitate phagocytosis, and 3) the membrane attack complex, which promotes cell lysis.

 

The absence of early components (C1-C4) of the complement cascade results in the inability of immune complexes to activate the cascade. Patients with deficiencies of the early complement proteins are unable to generate the peptides that are necessary clear immune complexes and to attract neutrophils or to generate to lytic activity. These patients have increased susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest autoimmune disease, of which complement deficiency may be an etiologic factor.

 

Approximately 30 cases of homozygous C4 deficiency have been reported. Most of these patients have systemic lupus erythematosus (SLE) or glomerulonephritis, IgA nephropathy. Patients with C4 deficiency may also have frequent bacterial infections and may present with autoimmune diseases such as SLE and SLE-like syndromes or rheumatoid arthritis. C4 is coded by two different genes in the major histocompatibility complex on human chromosome 6. Seventy-five percent of the population has two C4A and two C4B genes. However, the total sum of C4A and C4B genes in an individual can range from zero to 8 or more copies, giving this protein a wide range of concentrations and an even wider range of function in the general population. Most of the partial C4 deficiencies are without consequence, although deficiency of C4A is associated with a 15% incidence of SLE.

 

Complement levels can be detected by antigen assays that quantitate the amount of the protein (C4 / Complement C4, Serum). For most of the complement proteins, a small number of cases have been described in which the protein is present but is nonfunctional. These rare cases require a functional assay to detect the deficiency.

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.

22-45 U/mL

Interpretation
Provides information to assist in interpretation of the test results

Low levels of complement may be due to inherited deficiencies, acquired deficiencies, or due to complement consumption (eg, as a consequence of infectious or autoimmune processes).

 

Absent C4 levels in the presence of normal C3 and C2 values are consistent with a C4 deficiency.

 

Normal results indicate both normal C4 protein levels and normal functional activity.

 

In hereditary angioedema, a disorder caused by C1 esterase inhibitor deficiency, absent or low C4 and C2 values are seen in the presence of normal C3 (due to activation and consumption of C4 and C2).

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

Absent (or low) C4 functional levels in the presence of normal C4 antigen levels should be replicated with a new serum specimen to confirm that C4 inactivation did not occur during shipping.

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

1. Davis ML, Austin C, Messmer BL, et al: IFCC-standardization pediatric reference intervals for 10 serum proteins using the Beckman Array 360 system. Clin Biochem. 1996;29(5):489-492

2. Gaither TA, Frank MM: Complement. In: Henry JB, ed. Clinical Diagnosis and Management by Laboratory Methods. 17th ed. WB Saunders Company; 1984:879-892

3. O'Neil KM: Complement deficiency. Clin Rev in Allergy Immunol. 2000;19:83-108

4. Frank MM: Complement deficiencies. Pediatr Clin North Am. 2000;47:1339-1354

5. Brodszki N, Frazer-Abel A, Grumach AS, et al: European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management. J Clin Immunol. 2020 May;40(4):576-591

6. Willrich MAV, Braun KMP, Moyer AM, Jeffrey DH, Frazer-Abel A. Complement testing in the clinical laboratory. Crit Rev Clin Lab Sci. 2021 Nov;58(7):447-478. doi: 10.1080/10408363.2021.1907297

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

C4 activity is measured by mixing patient serum with a C4-deficient serum. The lytic activity of the serum mixture is tested against sensitized, labeled liposomes. If lysis occurs, the patient serum must be the source of the C4. The target liposomes are a commercial reagent (WAKO total complement CH50), and the assay is performed on an Advia XPT.(Unpublished Mayo method)

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.

Monday through Friday

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.

1 to 3 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 account representative. 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 was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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.

86161

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
C4FX C4 Complement, Functional, S 93978-5
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.
C4FX C4 Complement, Functional, S 93978-5

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