Induction of Systemic Lupus Erythematosus-like Disease in Mice by Immunization with Heparan Sulfate

Inflamed kidneys of NZB / W mice are a major site for the homeostasis of plasma cells

“…It has been shown in animal models and patients with various autoimmune diseases, that plasma cells in chronically inflamed tissues can produce antibodies specific for self-antigens [21][22][23]. The results presented here clearly demonstrate that the ASC in the kidneys of NZB/W mice are not restricted to self-antigens.…”

“…Clearly, due to their high numbers, the renal plasma cell infiltrates in NZB/W mice contribute to the development of hyper- gammaglobulinemia. Probably, they also contribute to the production of autoantibodies in these animals, as it has been shown for plasma cells located in chronically inflamed tissues of other autoimmune diseases, e. g. in BALB/c mice immunized with heparan sulfate, another animal model for SLE [23]. Indeed they may enhance the local concentrations of antibodies and immuncomplexes which finally lead to the observed severe destruction of the kidneys.…”

Development of Canine Systemic Lupus Erythematosus Model

“…Heparan sulphate could be one of the candidate autoantigens in SLE because it serves as a target antigen for in vivo cross‐reactive anti‐DNA antibodies (Suzuki et al., 1993). The mean IgG anti‐HS antibodies in sera of NZB/W F1 mice ( n = 10), 23 weeks old, ranged from O.D 0.73 to 2.14 (Ofosu‐Appiah et al., 1998). The reactivity of anti‐HS antibodies or cross‐reactive anti‐DNA antibodies with HS may induce glomerulonephritis by triggering inflammatory reactions locally.…”

“…IgG antibodies to HS in the sera and IgG antibodies to dsDNA (calf thymus DNA; Sigma D1501, treated according to the method of Ofosu‐Appiah et al., 1998) of control and HS‐immunized dogs were collected weekly (during 18 weeks) and were measured by enzyme‐linked immunosorbent assay (ELISA). For assay of anti‐HS antibodies, HS (bovine kidney; Sigma H7640, 2.5 μ g/well) was coated overnight at 25°C in PBS (pH 7.4, 1 m ) without pre‐coat.…”

“…As reactivity of serum antibodies with heparan sulphate (HS) in vitro (Faaber et al., 1986) and in vivo (Naparstek et al., 1999) has been associated with human and murine lupus, it has been suggested that autoimmunity to HS may be responsible for the induction of tissue damage and kidney dysfunction in SLE. Ofosu‐Appiah et al. (1998) investigated the ability of HS to initiate glomerulonephritis in murine SLE.…”