With new knowledge gained from molecular biology and hybridoma technology, as well as the original Witebsky postulates, we propose that three types of evidence can be marshalled to establish that a human disease is autoimmune in origin. They include direct evidence from transfer of pathogenic antibody or pathogenic T cells; indirect evidence based on reproduction of the autoimmune disease in experimental animals; and circumstantial evidence from clinical clues.

In 1957, at the dawn of the modern e~ a of research on autoimmunity, some rational steps were drawn up to establish the autoimmune etiology of human diseasesL They were consciously modelled on Koch's postulates, and required that an autoimmune response be recog nized in the form of an autoantibody or cell-mediated immunity; that the corresponding antigen be identified, and that an analogous autoimmune response be induced in an experimental animal. Finally, the immunized animal must also develop a similar disease. Stringent as they are, these steps still form a good basis for defining a human autoimmune disease. Now, 35 years later, a great deal of information has been gathered concerning the immune response and qutoimmunity, and the time has come to re-evaluate these original postulates in the light of current knowledge, particularly that acquired using molecular biology and hybridoma technology. On the basis of these developments, recent additional postulates have been put forward to define pathogenic iymphocytes mediating autoimmune diseases 2. This is especially timely since the original concept that autoreactivity is pathological has been challenged by numerous findings which demonstrate that self reactive lymphocytes represent a normal population of the immune system cell repertoire j, with only a small fraction of these representing pathogenic lymphocytes. Thus, the difference between'physiological'and'pathological'autoimmunity is now more sharply focused.