Breakdown products of C 3 in human synovial fluids.

Activation of the complement sequence results in conversion of the third component of complement (C'3) to an inactive product (C'3i) and the elaboration of additional fragments of smaller molecular weights and faster electrophoretic mobilities. Immunoelectrophoretic analysis of fresh synovial fluids with an anti-human C'3 antiserum disclosed in some a variable degree of conversion of C'3 to C'3i, but a more striking finding was an additional line in the alpha-globulin region. This faster migrating protein gave a reaction of partial identity with C'3/C'3i. With this antiserum a similar pattern developed when fresh human serum was incubated with immune complexes, or aggregated gamma-globulin. The same breakdown product of C'3 was obtained by treatment of fresh human serum with Zymosan, ammonium, hydrazine, agar, or dextran. Heating serum at 56 degrees C for 1 hr destroys the breakdown product; aging of serum produces it. Breakdown products of C'3 were looked for in 49 synovial fluids from patients with a variety of joint diseases. A significant correlation was found between the demonstration of the fast migrating breakdown product of C'3 and the diagnosis of rheumatoid arthritis and the presence of rheumatoid factor. A similar immunoelectrophoretic pattern was not found in the serum of any of the patients studied. When human gamma-globulin, which has been reduced and alkylated, is heat aggregated it loses the ability to fix human complement but still reacts with rheumatoid factor. Addition of reduced, aggregated gamma-globulin to fresh normal human serum produced no conversion of C'3, but when incubated with serum containing a high titer of rheumatoid factor, there was conversion of C'3 and the appearance of a breakdown product. Quantitative complement fixation studies with fresh serum from normal subjects and patients with rheumatoid arthritis disclosed complement fixation by reduced, aggregated gamma-globulin. The per cent of complement fixation was proportional to the titer of rheumatoid factor present in the test serum. These findings were interpreted as showing that rheumatoid factor can fix complement.The possibility is discussed that the presence of breakdown products of C'3 in the synovial effusions of most patients with seropositive rheumatoid arthritis and the ability of rheumatoid factor to fix complement are related phenomena.