Induction of systemic lupus erythematosus-like syndrome in syngeneic mice by immunization with activated lymphocyte-derived DNA

Abstract

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease and the mechanisms underlying the disease have not yet been elucidated. Thus, animal models of SLE would facilitate investigation of pathogenetic mechanisms involved in the development of the disease. This study characterizes a murine model of SLE-like syndrome induced by syngeneic activated lymphocyte-derived DNA (referred to as ALD DNA). Normal BALB/c mice were immunized subcutaneously with highly purified ALD DNA. Anti-double-stranded DNA (anti-dsDNA) antibodies were determined by enzyme-linked immunosorbent assay. Other SLE-associated autoantibodies were examined by indirect immunofluorescence and anti-ENA (extractable nuclear antigen) profile assay. Pathological changes were analysed by light microscopy and electron microscopy. Kidney cryostat sections were viewed by immunofluorescence for the presence of glomerular IgG and C3 deposits. Proteinuria was measured by Coomassie brilliant blue assay. High levels of anti-dsDNA antibodies and other autoantibodies frequently appearing in SLE were detectable in the sera of ALD DNA-immunized mice. Glomerulonephritis and glomerular deposition of IgG plus C3 were observed in the kidney sections. Moreover, proteinuria was seen in the immunized mice. SLE-like syndrome can be induced by ALD DNA in normal mice. This induced model may be useful for elucidating the mechanisms involved in autoimmunity to DNA and the development of SLE.