Sex hormone involvement in the induction of experimental systemic lupus erythematosus by a pathogenic anti-DNA idiotype in naive mice

The effect of sex hormones on the induction of experimental systemic lupus erythematosus (SLE) with a human anti-DNA (16/6 Id+) antibody, was studied. We found that injection of the pathogenic idiotype to BALB/c females and orchiectomized males treated with estrogen caused a rapid outburst of the disease 3 months after immunization, while nonestrogen treated mice developed the disease 5 months after immunization. The flare of SLE disease was characterized by raised levels of autoantibodies in the sera to dsDNA, histones, cardiolipin, Sm, RNP, SSA (Ro), SSB (La) and an emergence of high titers of mouse antibody carrying the 16/6 Id. These enhanced antibody levels were associated with an increase in erythrocyte sedimentation rate, proteinuria and leukopenia. Immunofluorescent studies confirmed the existence of immune complexes in the afflicted kidneys. Testosterone treated BALB/c females and orchiectomized males developed a classical response to the human anti-DNA antibody (16/6 Id+), but failed to develop fulminant SLE-like disease. Our data demonstrate the importance of sex hormones on the induction of experimental SLE-like disease in mice with no genetic tendency to autoimmunity.