The influence of aging on the induction and manifestations of experimental systemic lupus erythematosus

Abstract

The influence of age on autoimmunity was studied in a model in which experimental systemic lupus erythematosus (SLE) is induced in normal mice by the injection of a human monoclonal anti-DNA antibody expressing a common idiotype designated 16/6 Id. The resulting disease is expressed by the production of a variety of autoantibodies and clinical manifestations characteristic to human SLE. Female BALB/c mice, at ages of 2 and 12 months, were immunized with the 16/6 Id. Mice were tested periodically for the presence of autoantibodies. The production of all autoantibodies tested was significantly lower in the older mice as compared to the group of young mice. Clinical manifestations which included leukopenia, increased erythrocyte sedimentation rate and proteinuria were similar in both age groups. Kidney evaluations revealed differences among the two groups of mice. While in all kidney sections of young mice multiple immune complex deposits were detected, in the group of older mice half had similar pathology while the rest either were negative or had only segmental and partial glomerular immune complex depositions. Thus, aging is associated with a decrease in the capacity to respond to the pathogenic anti-DNA, 16/6 Id, by the production of antibodies and autoantibodies and in the expression of a milder disease.