C2 Complement, Antigen, Serum
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 classic pathway, 2) the alternative (or properdin) pathway, and 3) 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.
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.
Although rare, C2 deficiency is the most common inherited complement deficiency. Homozygous C2 deficiency has an estimated prevalence ranging from 1:10,000 to 1:40,000 (the prevalence of heterozygotes is 1:100 to 1:50). Half of the homozygous patients are clinically normal. However, discoid lupus erythematosus or systemic lupus erythematousus (SLE) occur in approximately 1/3 of patients with homozygous C2 deficiency. Patients with SLE and a C2 deficiency frequently have a normal anti-ds DNA titer. Clinically, many have lupus-like skin lesions and photosensitivity, but immunofluorescence studies may fail to demonstrate immunoglobulin or complement along the epidermal-dermal junction. Other diseases reported to be associated with C2 deficiency include dermatomyositis, glomerulonephritis, vasculitis, atrophodema, cold urticaria, inflammatory bowel disease, and recurrent infections.
Diagnosis of C2 deficiency
Investigation of a patient with an absent total complement (CH) level
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 C2 levels in the presence of normal C3 and C4 values are consistent with a C2 deficiency. Low C2 levels in the presence of low C3 and C4 values are consistent with a complement-consumptive process. Low C2 and C4 values in the presence of normal values for C3 is suggestive of C1 esterase inhibitor deficiency.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The total complement assay (see COM/8167 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 CH(50) level.
Complement levels also can be detected by functional assays. For most of the complement proteins, a small number of cases have been described in which the protein is present but is non functional. 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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and Management by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, WB Saunders Company, 1984, pp 879-892
2. O'Neil KM: Complement deficiency. Clin Rev Allergy Immunol 2000;19:83-108
3. Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47:1339-1354
4. Buckley D, Barnes L: Childhood subacute cutaneous lupus erythematosus associated with homozygous complement 2 deficiency. Pediatr Dermatol 1995;12:327-330