Serum factors in lupus erythematosus and other diseases reacting with cell nuclei and nucleoprotein extracts: electrophoretic. ultracentrifugal and chromatographic studies.

In the past decade much interest has been focused on the factors in human serum which in many ways resemble antibodies against components of cell nuclei. The lupus erythematosus (LE) cell, discovered by Hargraves, Richmond and Morton in 1948 (1), is now known to result from the interaction of leukocyte nuclei and a factor(s) most frequently found in the serum of patients with lupus erythematosus. Miescher (2) employed the y-globulin consumption test to demonstrate a reaction between factors in LE serum and isolated cell nuclei. Since this time, reactions between factors in LE serum and isolated cell nuclei (3, 4), intact nuclei in tissue sections (57), extracts containing nucleoprotein (8-10), nucleoprotein precipitates (11), preparations of desoxyribonucleic acid [DNA (4, 12-14)] and histone (15) have been demonstrated. The available information on the anti-DNA and other reactive factors in LE sera has been recently reviewed ( 16). As more information concerning the serum-cell nucleus interactions has become available, the nature and the significance of the phenomena have appeared more complex. Anti-cell nucleus factors have been found in the sera of patients with diseases other than lupus erythematosus (7, 11), in sera which do not contain detectable LE cell factor. It appears, therefore, that not all serum-cell nucleus interactions are of the kind that bring about the changes necessary for the production of LE cells. In addition, recent studies (17, 18) indicate that the source of the tissue used in making nucleoprotein extracts is an additional variable affecting the detection of serum anti-nucleus factors. Certain sera were found to react with a liver nucleoprotein component which was heat-stable and was destroyed by desoxyribonuclease, whereas other sera reacted with a heat-labile component of nucleoprotein extracts made from thymus tissue. The present study was undertaken, therefore, to characterize in physicochemical terms several of the serum anti-nucleus factors, to determine whether the serum factors reacting with what appear to be different nucleoprotein materials might differ also in other properties, and to determine the relationship of the anti-nucleoprotein factors to the LE cell factor and other anti-nucleus factors. Studies of the 'v-globulins in man have emphasized that they are composed of two groups of proteins with ultracentrifugal sedimentation coefficients of 6.6S (molecular weight about 160,000) or of 18S (molecular weight about 1,000,000) (19). These groups contain a range of differing molecules (20). Anion-exchange cellulose chromatography is a useful means of separating the 18S v-globulins from most of the 6.6S molecules and also provides a means for subdividing the 6.6S av-globulin group (20). By chromatographic means, antibody activities associated with 18S protein molecules have been separated from smaller 6.6S antibody molecules (21-24). In a preliminary report (24) on the anti-nucleus activities of LE sera, it was shown that certain anti-nucleus factors, presumably 18S 'v-globulins, could be separated by anion-exchange cellulose chromatography from the LE cell factor which appeared in this and other (3, 25, 26) studies to be within the 6.6S y-globulin group. The present report describes the electrophoretic, ultracentrifugal and chromatographic characterization of the factors in sera from patients with lupus erythematosus and other diseases which react with human leukocytes to form LE cells, with mouse liver cell nuclei as detected by fluorescein-labeled