Travels and travails of autoimmunity: a historical journey from discovery to rediscovery.

Consideration on autoimmunity began, as did immunology itself, around year 1900, first with Ehrlich's doctrine of 'horror autotoxicus', then interpreted as 'autoimmunity cannot happen'. Yet by 1904 the antibody nature of the autohemolysin responsible for cold hemoglobinuria was described, and soon confirmed, but without generating any durable concept on autoimmunization as a cause of disease. Reasons included Ehrlich's doctrine, the particular directions that immunology was to take after the initial advances, and a greater preoccupation with bodily responses to extrinsic rather than autologous substances. So, during 1915-1945, autoimmunity underwent a long eclipse despite, during this time, some potentially telling studies relating to brain, kidney and other diseases. The 'awakening' dates from 1945 when a general theoretical concept did appear feasible. Knowledge accrued from applications of several research undertakings mostly for purposes quite unrelated to the proof of autoimmunization: the use of adjuvants; the Coombes anti-globulin reaction; the Waaler-Rose rheumatoid factor; Hargraves' LE cell; the Witebsky-Rose experimental induction of thyroiditis with autologous thyroid gland, and others. By the early 1960s resistance to the idea of autoimmunization had weakened, perhaps hastened by a monograph on autoimmune disease published in 1963, and surely by the consensus reached at a large international conference published as proceedings in 1965. This present conspectus arbitrarily concludes at year 1965, recognizing that the history of autoimmunity even now is far from over.