Pioneering work by Noel Rose and Ernst Witebsky in New York, and Roitt and Doniach at University College London provided clear evidence that, at least in terms of antibody-producing B lymphocytes, diseases such as rheumatoid arthritis and thyrotoxicosis are associated with loss of immunological tolerance, which is the ability of an individual to ignore "self", while reacting to "non-self".
To establish that a disorder is an autoimmune disorder, Witebsky criteria requires that there be (1) a self-reactive antibody, (2) that a particular target for the antibody is identified (autoantigen) (3) that the disorder can be caused in animals and (4) that transferring antibodies from one animal to another triggers the disorder (passive transfer).
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