Treatment of lupus nephritis in adult (NZB + NZW)F1 mice by cortisone-facilitated tolerance to nucleic acid antigens.
AUTOR(ES)
Borel, Y
RESUMO
Adult female (NZB + NZW)F1 mice were treated with cortisone, cortisone with tolerogen (isologous NZB IgG-nucleosides conjugates) or cortisone with isologous IgG free of nucleosides. Other treatments also included tolerogen or isologous IgG alone, and cortisone together with denatured DNA. All untreated mice died by 10 mo of age. Cortisone prolonged the survival rate. This effect was further improved by combined treatment of cortisone and tolerogen. Prolonged survival was accompanied by a decrease in proteinuria. Other treatments failed to influence either survival or proteinuria. Although cortisone did not prevent the appearance of antibody to denatured DNA, cortisone and tolerogen suppressed them in most of the animals. Preexisting antibody to denatured DNA was reduced by cortisone and cortisone and tolerogen, but not by cortisone and IgG. In contrast, antibody to native DNA bore no relationship to therapy. Animals living beyond 1 yr of age, regardless of the treatment, fall into three histopathological categories: (a) severe nephritis, as in untreated animals, (b) moderate nephritis (with absence of severe alteration of the glomerular basement membrane, i.e. the histological counterpart of prolonged survival), (c) minimal nephritis. In a small number of animals treated with cortisone or cortisone and IgG and in 6/20 animals treated with cortisone and tolerogen, minimal lesions as judged by light, fluorescent, and electron microscopy were found. These last mice were in good health at 15-16 mo of age, twice the life-span of untreated mice. In conclusion, these data suggest that tolerance to nucleic acid antigens facilitated by cortisone offers a promising new approach to treat established murine lupus nephritis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=372537Documentos Relacionados
- Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice.
- Effect of low dietary lipid on the development of Sjögren's syndrome and haematological abnormalities in (NZB x NZW)F1 mice.
- Repetitive usage of immunoglobulin VH and D gene segments in CD5+ Ly-1 B clones of (NZB x NZW)F1 mice.
- Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA.
- Somatic diversification of the S107 (T15) VH11 germ-line gene that encodes the heavy-chain variable region of antibodies to double-stranded DNA in (NZB x NZW)F1 mice.