MicroVue™ C4d EIA

The MicroVue C4d EIA Assay is an enzyme immunoassay for the quantitation of the C4d-containing fragments of activated C4.

96 well plate with 12 eight-well strips in a resealable foil pouch

Serum 1.2–8.0 μg/mL, EDTA Plasma 0.7–6.3 μg/mL

Baboon

Store the unopened kit at 2°C to 8°C. Refer to Product Insert for additional storage details.

The MicroVue C4d Fragment Enzyme Immunoassay measures the amount of the C4d-containing activation fragments of C4 (C4b, iC4b, and C4d). The fourth component of complement is one of the plasma proteins that is unique to the classical pathway of complement activation. Classical pathway activation is triggered upon binding of the C1q subcomponent of C1 to IgG or IgM-containing immune complexes. In addition, C1 is bound and activated by a variety of other substances including retroviruses, certain bacteria, parasites, transformed cells, subcellular membranes, polyanions (DNA), and C-reactive protein in complex with phosphorylcholine. Binding of C1 to these activators of the classical pathway results in conversion of the zymogen C1s sub-component into an active proteolytic enzyme (C1s ). C1s cleaves the C4 α-chain at peptide bond 77 resulting in the production of C4a and C4b fragments with molecular weights of 9,000 and 191,000, respectively. The C4a fragment is one of the complement anaphylatoxins. The C4b fragment has numerous important biological activities. These activities include mediation of enhanced phagocytosis of complement-activating targets by white blood cells (opsonization) and participation in classical pathway C3 and C5 convertase assembly, which leads to terminal component activation and subsequent complement-mediated lysis of target microorganisms and other cells. The expression of the biological activities of C4b is strictly regulated. Thus, the ability of C4b to participate in classical pathway activation and opsonization reactions is inhibited by the single site cleavage of the C4b αchain by Factor I. This reaction requires either C4 binding protein (C4bp) or complement receptor CR1 as a cofactor. C4bp is a complement control protein and CR1 is the C3b/C4b receptor found on erythrocytes, granulocytes, monocytes, and macrophages. Factor I cleavage of C4b yields inactivated C4b, termed iC4b. iC4b can be further degraded by Factor I, with the cooperation of C4bp or CR1, to C4c and C4d fragments. The C4c and C4d fragments, which can be produced in fluid phase as well as on target surfaces, appear to be the final physiological degradation products of C4b. C4d has been quantitated in human serum and plasma specimens. The levels of C4d, when normalized for the presence of endogenous C4, can be significantly elevated in plasma specimens obtained from some patients with rheumatoid arthritis, hereditary angioedema, systemic lupus erythematosus, or chronic urticaria with hypocomplementemia. C4d levels may also be elevated in body fluids and plasma samples obtained from other patients in which classical complement pathway activation is known to occur, e.g., from patients with a variety of humoral autoimmune diseases, septicemia, thermal injury, multiple organ trauma, myocardial infarctions, hereditary angioedema, glomerulonephritis, and acute respiratory distress syndrome. The correlation between C4d activation fragment levels and the clinical status or prognosis for patients with these and other diseases remains to be determined.