Test Code LAB151 Complement C4, Serum
Reporting Name
Complement C4, SUseful For
Investigating an undetectable total complement
Confirming hereditary angioedema (with low C1 inhibitor)
Assessing disease activity in systemic lupus erythematosus, proliferative glomerulonephritis, rheumatoid arthritis, and autoimmune hemolytic anemia
Performing Laboratory

Specimen Type
SerumSpecimen Required
Supplies: Sarstedt Aliquot Tube 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
Specimen Type | Temperature | Time |
---|---|---|
Serum | Refrigerated (preferred) | 7 days |
Frozen | 28 days | |
Ambient | 72 hours |
Reference Values
14-40 mg/dL
Test Classification
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
86160
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
C4 | Complement C4, S | 4498-2 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
C4 | Complement C4, S | 4498-2 |
Clinical Information
The complement system is an integral part of the immune defenses. It can be activated via immune complexes (classic pathway) or by bacterial polysaccharides (alternative pathway). The classic complement pathway consists of recognition, (C1q, C1r, C1s), activation (C2, C3, C4), and attack (C5, C6, C7, C8, C9) mechanisms with respect to their role in antibody-mediated cytolysis. C4 is one of the activation proteins of the classic pathway.
In the absence of C4, immune complexes will not be cleared by C3 activation peptides, but bacterial infections can still be defended via the alternative pathway.
Complement component 4 may be decreased in systemic lupus erythematosus, early glomerulonephritis, immune complex disease, cryoglobulinemia, hereditary angioedema, and congenital C4 deficiency.
Interpretation
Complement component 4 levels will be decreased in acquired autoimmune disorders, in the active phase of lupus erythematosus, and in rheumatoid arthritis.
An undetectable C4 level (with normal C3) suggests a congenital C4 deficiency.
Levels will be increased in patients with autoimmune hemolytic anemia.
Cautions
The results are dependent on appropriate specimen transport.
Quantitation of specific proteins by nephelometric means may not be possible in lipemic sera due to the extreme light scattering properties of the specimen. Turbidity and particles in the specimen may result in extraneous light scattering signals, resulting in variable specimen analysis.
Clinical Reference
1. Willrich MAV, Braun KMP, Moyer AM, Jeffrey DH, Frazer-Abel A. Complement testing in the clinical laboratory. Crit Rev Clin Lab Sci. 2021;58(7):447-478. doi:10.1080/10408363.2021.19072972
2. Wong EKS, Kavanagh D. Diseases of complement dysregulation-an overview. Semin Immunopathol. 2018;40(1):49-64. doi:10.1007/s00281-017-0663-8
3. Prohaszka Z, Kirschfink M, Frazer-Abel A. Complement analysis in the era of targeted therapeutics. Mol Immunol. 2018;102:84-88. doi:10.1016/j.molimm.2018.06.001
4. 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;40(4):576-591. doi:10.1007/s10875-020-00754-1
Method Description
In this Siemens Nephelometer II method, the light scattered onto the antigen-antibody complexes is measured. The intensity of the measured scattered light is proportional to the amount of antigen-antibody complexes in the sample under certain conditions. If the antibody volume is kept constant, the signal behaves proportionally to the antigen volume.
A reference curve is generated by a standard with a known antigen content on which the scattered light signals of the samples can be evaluated and calculated as an antigen concentration. Antigen-antibody complexes are formed when a sample containing antigen and the corresponding antiserum are put into a cuvette. A light beam is generated with a light-emitting diode, which is transmitted through the cuvette. The light is scattered onto the immuno-complexes that are present. Antigen and antibody are mixed in the initial measurement, but no complex is formed yet. An antigen-antibody complex is formed in the final measurement.
The result is calculated by subtracting value of the final measurement from the initial measurement. The distribution of intensity of the scattered light depends on the ratio of the particle size of the antigen-antibody complexes to the radiated wavelength.(Instruction manual: Siemens Nephelometer II Operations. Siemens, Inc; Version 2.4, 07/2019)
Reject Due To
Gross hemolysis | OK |
Gross lipemia | Reject |
Gross icterus | OK |
NY State Approved
YesMethod Name
Nephelometry
Secondary ID
8171Specimen Retention Time
14 daysForms
If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.
Day(s) Performed
Monday through Friday