Autoimmunity to histones, ubiquitin, and ubiquitinated histone H2A in NZB x NZW and MRL-lpr/lpr mice. Anti-histone antibodies are concentrated in glomerular eluates of lupus mice.
In lupus diseases products of chromatin catabolism released from dead cells might be involved in the induction of autoantibody and in the development of glomerulonephritis. While the pathogenic role of anti-DNA antibodies is recognized, the role of antibodies directed against structural proteins of chromatin is still questioned. IgG antibodies to histones, ubiquitin, and ubiquitinated histone H2A (UH2A) have been investigated both in plasma and in glomerular eluates of NZB x NZW and MRL-lpr/lpr mice. In NZB x NZW mice, anti-ubiquitin and anti-UH2A antibodies were detected at 8 weeks of age, simultaneously with anti-double-stranded DNA antibodies, whereas anti-histone antibodies appeared later. In MRL-lpr/lpr mice, anti-DNA antibodies were detected at 4 weeks, whereas anti-histone, anti-ubiquitin, and anti-UH2A antibodies were not detected at that age but appeared in plasma rapidly thereafter. In both strains, increased anti-histone activity was found in IgG eluted from glomeruli. These results support the suggestion that anti-histone antibodies are likely to play a pathogenic role in lupus nephritis. They also indicate that, like human lupus, murine lupus is characterized by the production of anti-ubiquitin and anti-UH2A antibodies.