AUTOIMMUNE TUBULOINTERSTITIAL NEPHRITIS - INSIGHT FROM EXPERIMENTAL-MODELS

Many forms of tubulointerstitial nephritis (TIN) may have an autoimmun e origin. To understand the pathogenesis of autoimmune TIN it is impor tant to examine suitable animal models where the initiation and develo pment of tubulointerstitial diseases can be assessed with precision. E xperimental models of autoimmune anti-tubular basement membrane (anti- TBM) disease for example have allowed to define the nephritogenic role of antibodies which target tubulointerstitial moieties. Several tubul ointerstitial antigens which are recognized by specific anti-TBM antib odies have been characterized at a molecular level in these models. Th e CBA/CaH-kdkd mouse strain represents another model of TIN where comp lex T-cell networks are uniquely altered, resulting in cell-mediated i nterstitial nephritis. Characteristic tubular alterations (up-regulati on of adhesion molecules and CD44, cytokine and chemokine secretion) a re prominent in several models of experimental TIN, promoting T-cell a nd monocyte infiltration. The complex interplay between tubular epithe lial cells and immune cells is probably a prerequisite for a coordinat ed immune response in many forms of TIN, resulting in autoimmune renal tubulointerstitial injury and ultimately in renal failure.