ROLE OF ANTIGEN SIZE AND CHARGE IN IMMUNE-COMPLEX GLOMERULONEPHRITIS .1. ACTIVE INDUCTION OF DISEASE WITH DEXTRAN AND ITS DERIVATIVES

Abstract

To explore the role of size and charge in immune complex glomerulonephritis, a series of sized (10,000-, 70,000-, 500,000-dalton) dextrans was modified by the addition of charged groups (diethylaminoethyl dextran, neutral dextran, dextran sulfate) and administered to mice. The animals developed glomerulonephritis characterized by the deposition of IgA with lesser amounts of IgM and C[complement]3. The pattern of glomerular response was charge dependent with neutral antigens eliciting a focal, segmental proliferative response with mesangial deposition in scant amounts. The anionic dextran sulfate led to a diffuse mesangial proliferative picture with heavy deposition. The cationic, diethylaminoethyl-dextran-treated animals showed a marked increase in mesangial matrix with much less proliferation. The importance of this model to mechanisms of complex deposition, i.e., circulating vs. in situ, and the potential importance of polysaccharide antigens (this study representing the 1st active induction of nephritis with this class of substances) are discussed.