Activation of the Complement and Properdin Systems in Rheumatoid Arthritis*

The classic (C1, C4, and C2) and properdin factors (D, C3b, and B) of complement generate C3 convertases that are capable of cleaving C3 and subsequently activating C5-C9. Both C1 and factor D are serine esterases, and both convertases undergo decay and regeneration. In seropositive rheumatoid arthritis, where intraarticular activation of the classic early components (C1, C4, and C2) by immunoglobulin complexes appears to predominate, findings of relative depressions in synovial fluid levels of factor B indicate recruitment of the amplification loop (D, C3b, and B), and relative declines in properdin levels suggest activation of the properdin pathway as well. Quantitative analysis of the complement system in disease states requires several different approaches: measurement of function and antigenic concentration to assess the functional integrity of the protein; determination of component metabolism to appreciate the relative contributions of hypercatabolism and hyper- or hyposynthesis to the plasma level; and for compartmentalized disease, measurement of the component in the appropriate biologic fluid and determination of local tissue synthesis.