Detection and partial characterization of circulating immune complexes with solid-phase anti-C3.

Most antigen-nonspecific assays for immune complexes (IC) may simultaneously detect several non-IC substances that can interfere with accurate results. To overcome this flaw, we developed a solid phase assay that specifically detects complement-fixing IC. For this assay, test sera are reacted with matrix-bound F(ab′)2 anti-C3, and the amount of Ig bound is then measured with radioiodinated IgG anti-Ig. Thereby, one can detect as little as 6 µg of aggregated human γ globulin per milliliter of serum. By using species-specific reagents, the assay was adapted for testing sera from various species. High levels of IC were found in sera of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren’s and Reiter’s syndromes, acute glomerulonephritis, infectious endocarditis, and various types of malignancies. High concentrations of IC were also found in mice (NZB × W, BXSB, MRL/1) with spontaneous SLE-like syndromes and in rabbits with chronic serum sickness. Some of the IC-positive human serum samples contained complexes of heavy (>19S) and medium (8 to 19S) sedimentation rates, whereas other samples had predominantly a light (7 to 8S) material that interacted with F(ab′)2 anti-C3 and conglutinin. Studies on a small number of serum samples suggested that patients with less severe disease more frequently had the light anti-C3 reacting material, whereas patients with generalized severe disease more frequently had heavy complexes. The light material may comprise IgG antibody complexed with small C3 fragments generated during the solubilization of IC by complement.