All complement proteins are acute phase reactants and rise rapidly in concentrations during inflammatory episodes. Conversely, the rates of complement protein catabolism may greatly increase in various autoimmune diseases. Because complement component determinations represent a static measurement of the net concentrations that result from a dynamic balance between component synthesis and catabolism, serial sample quantitations are more clinically useful.
In most disease states, complement functions “normally” in producing inflammation and tissue damage. When complement plays a role in the development of a disease, it is often due to activation by an “abnormal” antibody, immune complex, or foreign material.
Increased C3 levels are associated with acute phase reaction, rheumatic disease, viral hepatitis, myocardial infarction, cancer, diabetes, pregnancy, sarcoidosis, amyloidosis, thyroiditis, inflammatory bowel disease, typhoid fever, and pneumococcal pneumonia. The magnitude of C3 increase is rarely more than two-fold and may mask decreases in levels due to concurrent consumption.
Decreased levels of C3 occur in individuals with congenital deficiency or immunologic diseases (where complement is consumed at an increased rate). C3 and/or complement C4 (C4) levels may be decreased in cases of: systemic lupus erythematosus (SLE) (especially with lupus nephritis), acute and chronic hypocomplementemic nephritis, infective endocarditis, disseminated intravascular coagulation (DIC) (especially with hemolytic uremic syndrome form), and partial lipodystrophy (with associated nephritis-like activity in serum). Cases of hereditary C3 deficiency, while rare, are characterized clinically by recurrent infection and by immune complex disease, in particular, membranoproliferative glomerulonephritis. The central role of C3 in both classical and alternate pathways, results in C3 deficient patients being at risk for especially severe infections by encapsulated bacteria such as S. pneumoniae, H. influenzae, and N. meningitidis. Bacteremia, sinopulmonary infections, meningitis, paronychia, and impetigo may occur. Deficient C3 levels have also been found in cases of uremia, chronic liver diseases, anorexia nervosa, and celiac disease.