The Clinical Laboratory: Testing the Complement System

Our current knowledge of the participation of complement in human disease and its biological importance in host defense is closely connected to progress in laboratory complement diagnosis. Although it is well documented that complement plays a decissive role in the pathogenesis of various diseases, it is somewhat surprising that achievements in complement research only find limited implementation in the clinic. Despite the presence of a broad spectrum of commercially available reagents, a comprehensive analysis of complement is still performed in only a few specialized laboratories. In most clinics, complement diagnosis is confined — as it was 20 years ago — to immunochemical determinations of C3 and C4, sometimes of factor B and C1 inhibitor (C1-INH), and is only occasionally extended to hemolytic titration of total functional activity (CH50). Rare, but clinically important complement deficiency states are thus frequently overlooked. The limited acceptance of complement assays as an essential part of laboratory diagnosis in various diseases may be explained by minor therapeutic consequences, due to the lack of reagents for specific pharmacologic intervention. Recent advances in the field of complement-directed therapy is expected to influence positively clinicians’ opinion on the necessity for complement diagnosis. The management of patients with autoimmune diseases or adverse reactions to drugs and artificial surfaces or those at risk from trauma-related syndromes such as adult respiratory distress syndrome (ARDS) and multiple organ failure, benefits from early diagnosis. There is still a substantial need for laboratory parameters as early markers of deleterious clinical conditions. Longitudinal studies of patients are of advantage. The clinician can observe changes in the complement profile which may be indicative of activation resulting from disease activity or clinical intervention. The utility of complement diagnosis for monitoring of disease activity has been extensively demonstrated in cases of systemic lupus erythematosus (SLE) [12, 36, 86, 106], and elevated plasma levels of complement activation products have been shown to be of prognostic value in recognizing patients with impending transplant rejection [87] and trauma-induced adult respiratory distress syndrome and multiple organ failure [51, 178, 188]. A complete complement profile provides valuable information in diagnosing the various forms of hypocomplementemic glomerulonephritis and may substantially aid in the interpretation of findings in renal biopsies [60, 181].