Objective. To assess whether nucleosome‐restricted antibodies, i.e., antibodies that react with the whole nucleosome particle but not with its individual components (double‐stranded DNA [dsDNA] and his‐tones), are present in the sera of patients with systemic lupus erythematosus (SLE).

Methods. Antibodies were detected by enzyme‐linked immunosorbent assay using purified nucleo‐somes, dsDNA, or histones. These tests were applied to the sera of 40 patients with SLE. Protein G–purified IgGs of representative sera were sequentially adsorbed on dsDNA‐and histone‐conjugated solid‐phase supports and further assayed for their nucleosome, dsDNA, and histone reactivities.

Results. Of the 40 sera tested, 16 displayed anti‐dsDNA and/or antihistone antibody activity, which was always associated with significant antinucleosome reactivity. In addition, 3 sera showed antinucleosome activity that was not associated with concomitant anti‐dsDNA or antihistone activity. The presence of true nucleosome‐restricted antibodies was demonstrated, after solid‐phase adsorption, in representative SLE sera that showed anti‐dsDNA or antihistone antibody activity, and also in sera that did not show these activities.

Conclusion. Our results provide evidence for the presence of nucleosome‐restricted antibodies in patients with lupus. These nucleosome‐restricted antibodies, along with anti‐dsDNA and antihistone antibodies, appear to belong to a broad set of antinuclear antibodies, the antinucleosome family.