Nucleosome‐restricted antibodies are detected before anti‐dsdna and/or antihistone antibodies in serum of mrl‐mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria

OBJECTIVE: To compare the humoral response to nucleosomes with the response to their individual components (double-stranded DNA dsDNA and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice. METHODS: We used enzyme-linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones. RESULTS: Antinucleosome antibodies emerged before anti-dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome-restricted antibodies were detected in the proteinuric MRL mouse kidney eluate. CONCLUSION: Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.