New ideas in the pathogenesis of nephritis.

Experimental work in the 1960's showed that in animals nephritis could be induced by two different methods-(i) reaction between antigen in the glomerular basement membrane (GBM) and antibody to it, the antibody arising either by immunisation of the host with autologous or heterologous GBM or by passive immunisation, and (ii) injection into the animal of foreign protein to cause acute (one injection) or chronic (repeated injections) immune complex disease. Thus models exemplifying antibody-mediated (type II) and immune complexmediated (type III) immune responses were established. Study of human nephritis showed that there are parallel disorders in the human kidney. Goodpasture's syndrome is characterised by a circulating antibody to GBM, transfer of which to primates reproduces the disease, and immunofluorescent study of the kidney shows the characteristic linear deposition of immunoglobulin and complement on the GBM. The evidence that immune complex disease occurs in man rests on appearances in the glomeruli similar to those in experimental animalsthat is, granular deposition of immunoglobulin and complement with the demonstration of an antibody to a defined antigen in the diseased glomeruli. The latter, more rigid criterion has been met in only a small number of instances. The involvement of mediators such as complement, polymorphonuclear leucocytes, fibrin and platelets in producing glomerular damage initiated by either antibody alone or antigen-antibody complexes has been the subject of intensive investigation during the last fifteen years, both in experimental animals and in humans. Although not every mediator system is necessarily involved in each form ofnephritis, bothtype IIand typeIIImechanisms cause only slight or moderate tissue damage without the participation of mediators. This article will briefly review recent additions to the knowledge outlined above and some of the current problems posed in trying to explain new data concerning nephritis. It will therefore not provide a comprehensive description of the pathogenesis of nephritis; this is outlined elsewhere.1-3