Recent studies have demonstrated that the factors responsible for the various serological reactions currently employed for the diagnosis of rheumatoid arthritis represent macroglobulins which, in the isolated state, have a corrected sedimentation coefficient of approximately 19S (1-5). In serum and plasma, these proteins exist as complexes with low molecular weight y-globtulins and show a higher sedimentation rate, approximately 22S (6, 7). It has become clear that the rheumatoid factors have a specific affinity for ordinary y-globulin showing a behavior, particularly in certain of the serological tests, like that of anti-y-globulin antibodies. The possibility has been raised that the rheumatoid factor complex in serum represents an antigen-antibody complex.During the course of investigation of the rheumatoid factors and their complexes through ultracentrifugal analyses of sera showing high titer reactions in the latex fixation test and y-globulin precipitin test, another group of y-globulin complexes was encountered. These had sedimentation rates between 9 and 17S and were dissociated in urea and acid buffers in a manner similar to the previously observed dissociation of the rheumatoid factor complexes. Again the question arises as to whether these are antigen-antibody comlplexes or simple aggregates of y-globulin.Gamma globulin components in the 9 to 12S range have been observed in many preparations of normal Fr II y-globulin. The (15,16), although the sedimentation rate of the main abnormal protein was lower than the 18 to 20S range of the proteins described by Waldenstr6m. Macroglobulins of the latter class are a homogeneous group and are known to be stable proteins which do not dissociate in urea and acid and alkaline buffers (17). They have specific immunological properties and dissociate in the presence of agents breaking disulfide bonds (18).In the present study, sera from 11 different patients, 7 with classical rheumatoid arthritis, were found to contain multiple y-globulin complexes. These were readily detected in whole serum and plasma by direct ultracentrifugal analysis. They did not possess rheumatoid factor activity but were associated in the same sera with large amounts of rheumatoid factor. Investigation of the association and dissociation reactions of these complexes was carried out and certain of their properties de-fined. Evidence for and against the hypothesis that they represent antigen-antibody complexes of the y-globlulin-anti-y-glol)bulin type was sought.
MATERIAL AND MIIETHODSSix of the 11 patients whose sera were specifically analyzed in this study were observed in the clinic and outpatient department of the Rockefeller Hospital. Three of the remainder represented patients in various New York 1-17