PATHOGENIC SERUM IGG ANTICARDIOLIPIN ANTIBODIES AND THE IDIOTYPIC NETWORK

Objectives-To determine whether active immunisation of mice with patho genic anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient with the antiphospholipid syndrome, could dysregulate th e idiotypic cascade and induce the production of anti-anti-anticardiol ipin (Ab3) with anticardiolipin activity by the mice with the associat ion of overt antiphospholipid syndrome. Methods-Anticardiolipin antibo dies were purified from the serum of a patient with the antiphospholip id syndrome. The purified anticardiolipin antibodies were used to immu nise mice at the footpads and the mice were then followed up for serol ogical and clinical manifestations of the antiphospholipid syndrome. R esults-The IgG anticardiolipin antibody was found to be monospecific a nd to bind cardiolipin with high affinity. Immunisation of naive BALB/ c mice with the purified IgG anticardiolipin antibody was followed by production in the mice of sustained high titres of IgG anticardiolipin antibody, associated with a prolonged activated partial thromboplasti n time (64.5 (9.7) v 30.1 (1.7) seconds in control mice) and thrombocy topenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/1 platelets in contro ls). The titres of other autoantibodies (for example, antibodies to DN A, histone), though high after the immunisation, decreased rapidly and were almost undetected one month after the boost injection. The mice immunised with the IgG anticardiolipin antibody showed low fecundity ( 36% of mice became pregnant v 62% in the group immunised with control IgG). The pregnant mice had an increased resorption rate (the equivale nt of fetal loss in the human) of 61 (9)%/ v 5 (4)% in the control gro up. The mean (SD) embryo and placental weights in mice with the antiph ospholipid syndrome were significantly lower than in the mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145 (8) mg respectively. The IgM anticardiolipin antibodies purified from the same patient were found to be polyspecific, binding with low affinity to anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA idiotype 16/6. Mice immunised with the purified IgM anticard iolipin antibodies. though showing reduced fecundity (30%), had only a slightly increased resorption rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non-significant decrease in mean (SD) embryo and placental weights (1134 (188) and 136 (11) mg respectively) . Conclusions-The results confirm the induction of pathogenic anticard iolipin antibodies by immunisation with serum anticardiolipin, dysregu lating the idiotypic network, and point to the higher pathogenic poten tial of serum IgG v IgM anticardiolipin antibodies.