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 antiglobulin 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.