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 res ponse to their individual components (double-stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies i n immune deposits in the kidney of MRL mice. Methods. We used enzyme-l inked immunosorbent assays of sera and kidney eluates for antibody act ivity against purified nucleosomes, dsDNA, and histones. Results. Anti nucleosome antibodies emerged before anti-dsDNA and antihistone antibo dies. 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 autoanti bodies and that antinucleosome antibodies might be involved in the nep hritogenic process in murine lupus.