C1 INH protein, C1 INH functional assay
ELISA / Addressable LASER Bead Immunoassay (ALBIA)
Dependent on Assay
Complement (C) proteins are components of the innate immune system. Complement can be activated by three ‘interacting’ pathways:
1) the classical pathway,
2) the alternative (or properdin) pathway,
3) the lectin (or mannan-binding lectin: MBL) pathway.
The classical pathway includes proteins that are typically activated by antigen/antibody (immune) complexes. An IgM molecule or two IgG molecules are sufficient to trigger this pathway initiated by C1q. This activation process includes an amplification loop primarily mediated by C3, with cleavage of complement proteins resulting in three main components:
1) anaphylatoxins (C3a, C5a) that promote blood vessel dilation and inflammation,
2) opsonization peptides (C3b) that attract neutrophils and enhance phagocytosis,
3) the membrane attack complex (MAC; sC5b-C9), which promotes targeted cell lysis.
A deficiency of early complement components (C1, C2, C3, C4) results in an inability of immune complexes to activate the complement cascade and generate the peptides that are necessary to clear immune complexes, to attract neutrophils to the site of complement activation and /or to generate the lytic activity on targets mediated by the MAC. Typically, these patients are susceptible to infections by encapsulated microorganisms such as Streptococcus pneumoniae, Neisseria meningitis, Haemophilus influenzae, and Streptococcus agalactiae (Group B Streptococcus). The membrane attack complex (MAC) is measured as the soluble circulating macromolecular complex sC5b-9. Some autoimmune diseases have been associated with complement deficiency (e.g., C1q, C2 and C4 deficiency in SLE). C2 deficiency is the most common deficiency. A global measure of complement status is derived from the hemolytic complement test for both the classical (CH50) and alternative (AH50) pathways.
Deficiencies of the “late” complement proteins (C5, C6, C7, C8, and C9) are unable to form the MAC and may have increased susceptibility to Neisseria infections. Autoantibodies to certain complement components are also important considerations: anti-C1q are seen in SLE where they are associated with active renal disease and anti-Factor H is associated with an important subset of atypical hemolytic uremic syndrome (aHUS). If aHUS is a consideration, ADAMTS13 activity and inhibitor tests can be ordered on our separate requisition.
Undetectable complement levels (lower than normal reference ranges) are typically seen in patients with specific component deficiencies. Decreased complement levels are found in infectious and autoimmune diseases due to fixation and consumption of complement. Acquired angioedema is related to A deficiency of C1 esterase inhibitor (C1-INH).