An unusual protein component of high molecular weight in the serum of certain patients with rheumatoid arthritis.

In the sera of a number of patients with rheumatoid arthritis an unusual, high molecular weight protein component could be detected by direct ultracentrifuge analysis of whole serum. This material sedimented more rapidly than the normal 19 S component and reached concentrations up to 340 mg. per cent. Similar components were not observed in a limited control series. The high molecular weight material was present in the gamma-globulin fraction of serum and joint fluid. It had an S20,(w) of approximately 22 S and could be dissociated into 2 fractions, one of which had a sedimentation coefficient of approximately 19 S. Evidence for a direct relationship between the 22 S component and the gamma-globulin precipitation test was obtained. The latter reaction was found to occur in the presence of altered, aggregated gamma globulin. Absorption of serum with altered gamma globulin removed the 22 S component. There also appeared to be a connection with the sheep cell agglutination reaction and the latex fixation test. The 22 S fraction was always observed in sera giving the most positive tests. Procedures of density gradient and repeated preparative ultracentrifugation demonstrated that each of these reactions was caused by a high molecular weight fraction. The relationship between the unusual protein complex and various 19 S gamma-globulins and 19 S antibodies is discussed.