Drug-induced
autoimmune diseases have two immunological peculiarities. Firstly, some
autoantibodies are present, which are virtually never seen in spontaneous human diseases and may be regarded as specific. This applies to antimitochondria antibody type 3 (anti M3) in the lupus-like syndrome caused by
Venocuran, to antimitochondria antibody type 6 (anti M6) in iproniazide-induced
hepatitis, to anti-
insulin antibody found
after treatment with
methimazole, and to
anti liver/kidney microsome antibody type 2 (anti LKM2) associated with
hepatitis induced by tielinic
acid. Secondly, a search for other
autoantibodies shows that the
immune disorder is much more limited than in spontaneous
autoimmune diseases. Thus, contrary to myasthenia and idiopathic
autoimmune haemolytic anaemia, we never found
autoantibodies specifically directed against the thyroid, the stomach or the adrenal gland during treatment with
D-penicillamine and
alpha-methyldopa. Only some hypotheses may account for these peculiarities. Cross-reaction between
drug and
autoantigen may occur, but the fact that the antigen-antibody reaction is not inhibited by the
drug or its metabolites does not support this explanation. Much more attractive is the "T-cell bypass" theory, according to which autoreacting suppressor T-cells are circumvented by helper T-cells stimulated by the
drug-modified
autoantigen. In this case, the autoimmune reaction would indicate to which body substance the
drug is bound, thus making it
immunostimulant, and not a structural similarity between the
drug and the
autoantigen.