Autoantibodies and nephritis: different roads may lead to Rome

Our understanding of antibody-mediated renal damage has not changed drastically in recent years. However, within this framework a lot of new data emerged to change our way of looking at old diseases. For example, APSGN, which in the past has been regarded as a typical CIC-mediated disease, may also show ICs formed in situ. In Goodpasture's syndrome, once considered to be the classical model of autoantibody-mediated disease, it is now realized that nephritogenic T cells play an important role. Complement, formerly thought to be a pathogenic factor in nephritis, is now believed to be crucial for the protection of immune-mediated renal injury. At the same time, components of the fibrinolytic system play a role as autoantibody targets in renal damage, and a disregulation of this pathway may be a mechanism in different renal diseases. Furthermore, new hypotheses are emerging to explain how the immune system interacts with the external world. One of them suggests that a great deal more is involved than the mere discrimination between self and nonself: the immune system is able to handle all elements, even endogenous ones, that pose a potential danger to the host (Matzinger, 1994). Thus, tissues themselves play a central role: when healthy, they may induce tolerance and when distressed, they may stimulate immunity. In this view, autoimmunity can be regarded as a defect in the cross-talk between the immune system and the body tissues, a perspective that opens up fascinating new avenues for research on the mechanisms that regulate the expression of renal antigens in health and disease.