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The complement sequence consists of classical and alternate (Properdin) pathways which may be activated sequentially by a number of different causes. In general, the classic pathway is activated by antigen-antibody and cell antibody complexes and the alternate pathway by bacteria, fungi and some immune complexes. The sequence of activation in the classical pathway is C1, C4, C2, C3 and C5 to C9. In the alternate pathway C1, C4 and C2 are bypassed and C3 is activated by an initiating factor (IF), and two substances called Properdin Factors D and B. The most frequently occurring alterations of complement are increased levels, since most complement proteins are acute phase reactants. The main clinical application of complement assays is the detection of decreased levels, which may indicate an on going immunological disorder. Total hemolytic complement (CH50) is the best functional assay of the complete complement sequence. CH50 is often decreased in SLE, glomerulonephritis and other immune complex diseases. A normal CH50 level indicates that all the components, C1 through C9, are present. However, individual complement factors may be depleted 50 to 80% without affecting CH50 activity. Depletion of alternative factors is not detected. For this reason, it may be necessary to measure individual complement components. C3 protein is the key molecule in both the classical and alternative pathways and is present in the highest concentration. Decreased levels of both C3 and C4 indicate classical pathway activation. Decreased C3 levels with normal C4 levels indicate alternate pathway activation. Very low or undetectable levels of C4 with normal or relatively normal levels of C3 are often seen in type II cryoglobulinemia, which is most commonly associated with hepatitis C infection. Generally, decreased levels of individual complement proteins are due to increased catabolism. Because synthesis of complement proteins increases with inflammatory disease, normal levels do not prove that the complement sequence is not involved in tissue injury. Body fluid CH50 activity should normally be approximately one third to one half of the serum value. Decreased CH50 titers and complement protein levels may be seen in the joint fluid of patients with rheumatoid arthritis, gout, pseudogout, Reiters syndrome and gonococcal arthritis. Serum levels in these patients may be normal or increased. Specimen requirement is one 10 mL plain red top tube. Blood must be delivered to the laboratory within one hour. If prompt delivery is not possible, serum should be frozen and shipped in a plastic vial on dry ice. Reference ranges are: Serum, CH50 142 279 CH50 units/mL Serum, C3 83 172 mg/dL Serum, C4 14 40 mg/dL Body Fluids 1/3 to 1/2 serum level. |
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