Chronic Graft-versus-Host Autoimmune Disease in Fc Receptor γ chain-deficient Mice Results in Lipoprotein Glomerulopathy

Abstract

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.