Diagnosis of C3 deficiency
Investigation of a patient with undetectable total complement level
Automated Liposome Lysis Assay
C3
Complement
Functional C3
Functional Complement
Hemolytic C3
Hemolytic Complement
Third Component of Complement
Serum Red
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.
0.5 mL
Gross hemolysis | OK |
Gross lipemia | Reject |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum Red | Frozen | 14 days |
Diagnosis of C3 deficiency
Investigation of a patient with undetectable total complement level
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 (MAC), 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 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 in which complement deficiency may be an etiologic factor.
C3 is at the entry point for all 3 activation pathways to activate the MAC. C3 deficiency may result in severe and recurrent pneumococcal and neisserial infections. Deficiency is very rare, with less than 30 cases described.
Complement levels can be detected by antigen assays that quantitate the amount of the protein (C3 / Complement C3, 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.
21-50 U/mL
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 C3 levels in the presence of other normal complement values are consistent with a C3 deficiency.
Absent (or low) C3 functional levels in the presence of normal C3
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 Allergy Immunol. 2000;19:83-108
4. Frank MM: Complement deficiencies. Pediatr Clin North Am. 2000;47(6):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;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
C3 complement activity is measured by mixing patient serum with a C3-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 C3. The target liposomes are a commercial reagent (WAKO total complement CH50), and the assay is performed on Advia XPT.(Unpublished Mayo method)
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.
86161
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
C3FX | C3 Complement, Functional, S | 87723-3 |
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.
|
---|---|---|
C3FX | C3 Complement, Functional, S | 87723-3 |