In 1984, Proceedings of the Society for Experimental Biology and Medicine published a Minireview entitled “Autoimmune Diseases of the Kidney'”(1). The focus of the present update is on new antigen(s) (Ag[s]) and epitopes which incite the nephritogenic autoimmune response with or without tissue damage, their genetic requirements, and the evidence that T cells are involved not only in helping B cells synthesize autoantibodies but also in the development of tissue injury. As in the previous Minireview, we will consider the pathogenesis of spontaneous and experimentally induced autoimmune diseases in laboratory animals and the evidence, frequently partial or tentative, that similar pathogenetic mechanisms operate in humans.
Diseases Induced Mainly by Antibodies Reactive with Structural Antigens
Glomerular Basement Membrane.
Goodpasture disease. Antigen. The nephritogenic epitope is in type IV collagen of the glomerular basement membrane (GBM), alveolar basement membrane (ABM), and testicular basement membrane and lens, as shown in humans, cattle, and small laboratory animals. Type IV collagen is the scaffold of basement membranes, in combination with other macromolecular components, such as laminin, heparan sulfate proteoglycans, and enctactin. Type IV collagen is formed by building block units (protomers) that are linked to one another by end-to-end bonds. The protomers are composed of six genetically distinct α-chains characterized by three structural domains, the amino terminus (7S), the central helical region, and the NC1 (non collagenous) domain at the carboxyl terminus. At the NC1 junction, the NC1 domains (monomers) of the six α-chains form a hexamer. The antibodies (Abs) of Goodpasture patients or animals with experimentally induced Goodpasture disease bind to the NC1 domain of the α3-chain (α3[IV]) (2–4). The epitope is tentatively localized in the carboxyl terminus of the NC1 domain of α3(IV), encompassing residues 198–233 as the primary interaction site (5, 6).
