Pulmonary artery
thrombosis and an anti-ethinyl-
oestradiol monoclonal IgGlambda were found to be associated in a 36-year-old woman (Mrs MAI.) who took an
oral contraceptive containing 50 mug ethinyl-
oestradiol and 500 mug nor-
ethisterone daily. After appropriate purification including methods by which the
IgG was separated of bound circulating
hormones, its binding activity was demonstrated by several methods: passive haemagglutination of
oestradiol-
benzoate sensitized red blood cells; gel filtration on
Sephadex G-25; ultracentrifugation and equilibrium dialysis. IgGlambda MAI bound ethinyl
oestradiol (Ka=2-7 X 10(1) M-1) and also 17-beta-oestradiol, with a lower affinity (Ka=0-4 X 10(7) M-1). The valency for these two
hormones was near 2. Ethinyl-
oestradiol bound to the
IgG was displaced by ethinyl-
oestradiol itself and in decreasing order of potency by 17-beta-oestradiol,
progesterone, oestriol, and
testosterone. Oestrone and
hydrocortisone had no effect. Although the localization of the binding sites of this IgGlambda was not studied, it is likely that they were the antibody sites of the molecule and, according to immunochemical criteria, it may be classified as a monoclonal anti-ethinyl-
oestradiol antibody. It is felt that its association with the pulmonary
thrombosis and the
oral contraceptive may be significant. This supports the hypothesis of an immunological mechanism for the unexplained thrombotic risk of
oral contraceptives.