Relation of high molecular weight proteins to the serological reactions in rheumatoid arthritis.

The ability of sera from patients with rheumatoid arthritis to potentiate the agglutination of sensitized particulate bodies has been recognized since Cecil, Nicholls, and Stainsby (1931) noted the agglutination of certain strains of streptococci by these sera. More recently this property has been employed as the basis of a number of clinical tests for the diagnosis of rheumatoid arthritis. The tests most frequently used are the sensitized sheep cell agglutination, Fraction II agglutination, latex fixation, Rh agglutination, and gamma-globulin precipitation tests. The reaction common to all these tests seems to be the interaction of the rheumatoid factor or factors present in serum with gamma-globulin attached to a particulate body. The particulate body probably acts only as a carrier for the gammaglobulin since it has been demonstrated by Epstein, Johnson, and Ragan (1955) that Fraction II gammaglobulin can form a precipitate with rheumatoid sera directly. This is especially true when the gammaglobulin has previously been altered by heating or a number of other procedures (Franklin, Holman, Mifller-Eberhard, and Kunkel, 1957). Normal human gamma-globulin contains two major ultracentrifugal components. The main one has a sedimentation rate of 7S, while the minor one, which normally makes up from 5 to 10 per cent. of the total gamma-globulin, has a sedimentation coefficient of 19S (Muller-Eberhard, Kunkel, and Franklin, 1956). It has been demonstrated by numerous observers, particularly Svartz and Schlossman (1954) and by Ziff, Brown, Lospalluto, Badin, and McEwen (1956), that the rheumatoid factor is a gamma-globulin and that it can be concentrated in the euglobulin fraction of serum. Since the euglobulin fraction is rich in the minor high molecular weight fraction of gamma-globulin, it seemed