Induction of systemic lupus erythematosus-like disease in mice by immunization with heparan sulfate.

Experimental systemic lupus erythematosus (SLE)-like disease was induced in BALB/c mice by immunization with heparan sulfate, the major glycosaminoglycan of glomerular basement membrane. Following booster injections with heparan sulfate (HS), high levels of anti-HS, anti-dsDNA, and anti-cardiolipin antibodies were detected in the sera of the immunized mice. An enzyme-linked immunospot (ELISPOT) assay indicted that IgG anti-HS and anti-dsDNA antibody-secreting cells were present in the kidneys and most likely contributed to antibody localization. Antibodies eluted from the kidneys of immunized mice were found to react strongly with HS and dsDNA when tested in vitro. The HS-immunized mice developed moderate to severe levels of proteinuria. Histologic examination of kidneys from HS-immunized mice revealed deposition of immunoglobulin in the kidneys. Our results describe the induction of SLE-like disease in normal mice following immunization with HS. This experimental model may be useful for understanding the immunologic basis for autoimmunity to HS.