Diagnosis of C5 deficiency
Investigation of a patient with an absent total
Nephelometry
C5
C5 antigen
C5 level
Complement
Complement level
Fifth Component of Complement
Serum
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.
Patient Preparation: Fasting for 12 hours is preferred but not required.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
0.5 mL
Gross hemolysis | OK |
Gross lipemia | Reject |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Ambient | 7 days | |
Refrigerated | 28 days | ||
Frozen (preferred) | 60 days |
Diagnosis of C5 deficiency
Investigation of a patient with an absent total
Complement proteins are components of the innate immune system. There are 3 pathways to complement activation: the classic pathway, the alternative (or properdin) pathway, and the lectin activation (mannan-binding protein: MBP) pathway. The classic pathway of the complement system is composed of a series of proteins that are activated in response to the presence of immune complexes. The activation process results in the generation of peptides that are chemotactic for neutrophils and that bind to immune complexes and complement receptors. The end result of the complement activation cascade is the formation of the lytic membrane attack complex (MAC).
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 clear immune complexes or to generate lytic activity. These patients have increased susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest autoimmune disease, and complement deficiency may be an etiologic factor in the development of autoimmune disease.
More than 30 cases of C5 deficiency have been reported. Most of these patients have neisserial infections.
10.6-26.3 mg/dL
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 C5 levels in the presence of normal C3 and C4 values are consistent with a C5 deficiency. Absent C5 levels in the presence of low C3 and C4 values suggest complement consumption.
A small number of cases have been described in which the complement protein is present but is nonfunctional. These rare cases require a functional assay to detect the deficiency; for more information see C5FX / C5 Complement, Functional, Serum.
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.
1. Sonntag J, Brandenburg U, Polzehl D, et al. Complement system in healthy term newborns: reference values in umbilical cord blood. Pediatr Dev Pathol. 1998;1(2):131-135
2. Prellner K, Sjoholm AG, Truedsson L. Concentrations of C1q, factor B, factor D and properdin in healthy children, and the age-related presence of circulating C1r-C1s complexes. Acta Paediatr Scand. 1987;76(6):939-943
3. Davis ML, Austin C, Messmer BL, Nichols WK, Bonin AP, Bennett MJ. IFCC-standardized pediatric reference intervals for 10 serum proteins using the Beckman Array 360 system. Clin Biochem. 1996;29(5):489-492
4. Gaither TA, Frank MM. Complement. In: Henry JB. Clinical Diagnosis and Management by Laboratory Methods. 17th ed. Saunders; 1984:879-892
5. O'Neil KM. Complement deficiency. Clin Rev Allergy Immunol. 2000;19(2):83-108
6. Frank MM. Complement deficiencies. Pediatr Clin North Am. 2000;47(6):1339-1354
7. Volokhina EB, van de Kar NC, Bergseth G, et al. Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome. Clin Immunol. 2015;160(2):237-243.
8Andreguetto B, Murray D, Snyder M, Tostrud L, Willrich MA. Abstract 003: The impact of eculizumab in complement assays. Mol Immunol. 2015;67:119-120. doi:10.1016/j.molimm.2015.03.013
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.(Unpublished Mayo method; Instruction manual: Siemens Nephelometer II Operations. Siemens, Inc; Version 2.4, 07/2019)
Monday through Friday
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.
86160
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
C5AG | C5 Complement, Antigen, S | 4505-4 |
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.
|
---|---|---|
C5AG | C5 Complement, Antigen, S | 4505-4 |
Change Type | Effective Date |
---|---|
Test Status - Test Resumed | 2025-03-04 |
Test Status - Test Down | 2024-12-30 |