Autoimmune Target in Heymann Nephritis Is a Glycoprotein with Homology to the LDL Receptor

• DOI: 10.1126/science.2786251
• Publication Date: 2006-10-05T21:21:28Z
• Authors: Raktima Raychowdhury; John L. Niles; Robert T. McCluskey; John A. Smith
• Keywords: 0301 basic medicine; Membrane Glycoproteins; Molecular Sequence Data; Heymann Nephritis Antigenic Complex; DNA; Rats; 3. Good health; 03 medical and health sciences; Glomerulonephritis; Receptors, LDL; Rats, Inbred Lew; Reference Values; Sequence Homology, Nucleic Acid; Animals; Humans; Amino Acid Sequence; Autoantibodies

The pathogenesis of Heymann nephritis, a rat model of human membranous glomerulonephritis, depends on the interaction of autoantibodies with a renal glycoprotein (GP330) on glomerular podocytes. Partial complementary DNAs coding for GP330 were isolated and sequenced. The deduced amino acid sequence from 4.3 kilobases of complementary DNA contains the sequences identical to two peptides derived from the isolated glycoprotein. The deduced amino acid sequence of this protein contains regions with homology to the human low density lipoprotein (LDL) receptor, an indication that GP330 and the LDL receptor may be members of the same gene family. Autoantibodies from the kidneys of rats with Heymann nephritis reacted with a nonglycosylated segment of GP330 that contains cysteine-rich 40-amino acid repeats, which are also features of the LDL receptor. GP330 is also similar in some regions to the mouse epidermal growth factor precursor.