Plasma proteinase regulation during disease progression in murine models of SLE

Analysis of plasma proteinase during disease progression in murine models of systemic lupus erythematosus revealed three different patterns of regulation. Female NZB/W mice exhibited no age-dependent alterations in plasma proteinase activity from 3-9 months of age. Animals at nine months of age exhibited splenomegaly, high titers of serum autoantibodies and evidence of kidney disease, but no disruption of plasma proteinase activity. Male BxSB mice exhibited elevations in plasma proteinase activity as a late-onset (greater than 20 weeks of age) feature of the disease process. The onset of proteinase dysregulation occurred after significant mortality was evident and therefore variables associated with the induction of elevated levels of plasma proteinase activity are not related to early mortality factors. In contrast, female MRL-lpr mice exhibited age-dependent induction of elevated plasma proteinase activity which correlated temporally with the onset of mortality and the previously described reticuloendothelial system activation (Hart, J. Clin. Lab. Immunol., 26, 129). Interestingly, male MRL-lpr mice, which live slightly longer than female mice of the same strain, exhibited a delayed onset of plasma proteinase dysregulation. These results indicate that induction of changes in plasma proteinase regulation during the natural course of disease varies between these three murine models of SLE. Assessment of plasma proteinase regulation in human disease may reveal subpopulations of patients with features analogous to the murine models, which in turn could influence the choice of therapeutic modalities in disease management.