Autoimmune Disease
In an animal model, targeted deletion of fgl2 resulted in enhanced reactivity of innate and adaptive immune responses of DC, T and B cells. This increased immune reactivity was associated with development of autoimmune glomerulonephritis. Wild-type recipients reconstituted with bone marrow from fgl2-/- mice also developed autoimmune disease but fgl2-/- that were reconstituted with wild-type cells did not. With age, fgl2-/- mice lost weight and by 6 months, 25% of fgl2-/- aged mice developed severe glomerulonephritis, with characteristically small and yellow kidneys staining of kidneys with PAS reaction revealed extensive infiltration of mononuclear cells and interstitial fibrosis. Many renal tubules had collapsed and were surrounded with fibrin, and mesangial expansion was evident in the glomerulus. Hemosiderin staining of macrophages indicated the presence of hemorrhage within the kidney. Such kidney defects were not observed in wildtype mice at any age up to 9 months (Published in Shalev et al., J. Immunol., 2008 ). In fgl2-/- mice by 6 months the glomerular changes were severe and widespread with generalized increase in cellularity, marked mesangial thickening and marked decrease in vascularity. Additionally, at 6 months there was also a heavy interstitial inflammatory cell infiltration comprised predominantly of lymphocytes. There was also marked tubular loss, interstitial sclerosis, and fibrosis. Immunoperoxidase staining for IgG, IgM, and IgA was strongly positive in glomeruli and in infiltrating cells. Kidneys from wild-type mice were normal at all times. C3 deposits were detected in kidneys from fgl2-/- mice at 1, 3, and 6 months coincident with deposits of immunoglobulins. Urine and serum analysis was also performed at different time points and revealed progressive increases in the levels of protein (albumin) and blood in the urine and increases in serum creatinine in fgl2-/- mice with age. In contrast, in wild-type mice, the levels of albumin and blood in the urine and serum creatinine were normal at all times (Published in Shalev et al., J. Immunol., 2008 ).