Morphological analysis of autoimmune disease in MRL-lpr,Yaa male mice with rapidly progressive systemic lupus erythematosus.

We analyzed morphologically autoimmune disease in MRL/MpJ mice bearing both the Yaa and lpr genes (MRL-lpr,Yaa mice), and compared it with that in MRL/MpJ-lpr/lpr (MRL-lpr) mice, in order to examine the effect of the Yaa gene on lpr-induced tissue-specific immunopathologies. MRL-lpr,Yaa male mice developed glomerulonephritis more rapidly than did MRL-lpr males. The glomerular damage in MRL-lpr,Yaa males, as evaluated by histologic and immunofluorescent methods, was significantly greater than that in age-matched MRL-lpr males. In contrast, no differences in the development of vasculitis and arthritis were noted between the two groups. Pathological examination of the dead mice revealed a similar incidence of lethal glomerulonephritis in the two groups. Lymphoid hyperplasia in the spleen consisted predominantly of unusual T cells (B220+, Thy-1+, CD4-, CD8-) in the two groups, and an increased number of B cells was not found in MRL-lpr,Yaa mice. The histological nature of the autoimmune diseases was similar in MRL-lpr,Yaa and MRL-lpr males. These results indicate that the Yaa gene accelerates the development of glomerulonephritis but not that of vasculitis or arthritis, suggesting that the mechanisms underlying the initiation of glomerulonephritis are different from those leading to vasculitis or arthritis in MRL-lpr mice.