26506 C2 Complement, Functional, Serum (C2FXN)

​C2 Functional​​​

​Investigation of a patient with a low (absent) hemolytic complement.

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.

To evaluate for complement C2, C3, and C4 in one orderable, consider ordering C2 / C2 Complement, Functional, with Reflex, Serum.​

​1. Immediately after specimen collection, place the tube on wet ice.

2. Centrifuge and aliquot serum into plastic vial.

3. Immediately freeze specimen.

​As with all complement assays, proper sample handling is of utmost importance to ensure that the complement system is not activated before clinical testing.​

​​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. This 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, C2, C3, 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. They may also have symptoms that suggest autoimmune disease in which complement deficiency may be an etiologic factor.

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-double-stranded 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 of nearly zero, with normal values for C3 and C4.

​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 (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.