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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. This activation process results in the formation of the lytic membrane attack complex, as well as the generation of activation peptides that are chemotactic for neutrophils and that bind to immune complexes and complement receptors. The absence of early components (C1, C2, 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 lytic activity or to clear immune complexes.
Although rare, C2 deficiency is the most common inherited complement deficiency. Homozygous C2 deficiency has an estimated prevalence ranging from 1 in 10,000 to 1 in 40,000 (the prevalence of heterozygotes is 1 in 100 to 1 in 50). Half of the homozygous patients are clinically normal.
However, discoid lupus erythematosus or systemic lupus erythematosus (SLE) occurs in approximately one-third 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.
The laboratory findings that suggest C2 deficiency include a hemolytic complement (CH50) of nearly zero, with normal values for C3 and C4.
The investigation of a patient with a low (absent) hemolytic complement (CH50)
Absent (or low) 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.
Absent (or low) C2 functional levels in the presence of normal C2 antigen levels should be replicated with a new serum specimen to confirm that C2 inactivation has not occurred during shipping.
If requested not to reflex low C2 result specimens for C3 and C4 testing, the following comment will be reported; "C2 result is decreased. This could be a result of an inherited C2 deficiency, complement consumption, or C1 esterase inhibitor or deficiency. Analysis of C3 and C4 would be required for further interpretation."
1. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and Management by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, PA, WB Saunders Company, 1984, pp 879-892
2. Agnello V: Complement deficiency states. Medicine 1978;57:1-23
3. Buckley D, Barnes L: Childhood subacute cutaneous lupus erythematosus associated with homozygous complement 2 deficiency. Pediatr Dermatol 1995;12:327-330