During the past 50 years, systemic lupus erythematosus (SLE) has been the main subject in the field of immunopathology. Each individual discovery was followed by the discovery of a multitude of related immune phenomena. Thus, the false-positive VDR reaction opened the door to additional antibodies leading to the concept of the anti-phospholipid syndrome. The demonstration of anti-nuclear antibodies led to the discovery of a cascade of antibodies against various constituents of the cell nucleus. Today’s concept of a genetic predisposition emerged with the discovery of the H2 system in mice by Snell and subsequently of the immune response genes by Benacerraf and McDevitt.