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. 1976 Jun;24(3):455–463.

Oral contraceptive, pulmonary artery thrombosis and anti-ethinyl-oestradiol monoclonal IgG.

J L Beaumont, N Lemort
PMCID: PMC1538533  PMID: 820501

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson F. D., Schultz J. S. Oral contraceptive side-effects and allergy: an immune etiology? Lancet. 1971 Dec 18;2(7738):1374–1375. doi: 10.1016/s0140-6736(71)92390-7. [DOI] [PubMed] [Google Scholar]
  2. Baulieu E. E., Raynaud J. P. A "proportion graph" method for measuring binding systems. Eur J Biochem. 1970 Apr;13(2):293–304. doi: 10.1111/j.1432-1033.1970.tb00931.x. [DOI] [PubMed] [Google Scholar]
  3. Baulieu E. E., Raynaud J. P., Milgrom E. Measurement of steroid binding proteins. Acta Endocrinol Suppl (Copenh) 1970;147:104–121. doi: 10.1530/acta.0.065s104. [DOI] [PubMed] [Google Scholar]
  4. Beaumont J. L. Auto-immune hyperlipidemia. An atherogenic metabolic disease of immune origin. Rev Eur Etud Clin Biol. 1970 Dec;15(10):1037–1041. [PubMed] [Google Scholar]
  5. Beaumont J. L., Baudet M. F., Delplanque B., Péron F. L'hemagglutination passive au chlorure de chrome. Son emploi sans diluant macromoléculaire. Pathol Biol (Paris) 1969 Apr;17(7):429–434. [PubMed] [Google Scholar]
  6. Beaumont J. L., Delplanque B. Méthode de purification d'anticorps de lapin anti beta lipoprotéine humaine à partir de précipités spécifiques. Immunochemistry. 1969 May;6(3):489–494. [PubMed] [Google Scholar]
  7. Beaumont J. L. L'activité spécifique des protéines M. "Vers un nouveau critère de classification des myélomes et des macroglobulinémies". Rev Fr Etud Clin Biol. 1967 Apr;12(4):319–321. [PubMed] [Google Scholar]
  8. Bole G. G., Jr, Friedlaender M. H., Smith C. K. Rheumatic symptoms and serological abnormalities induced by oral contraceptives. Lancet. 1969 Feb 15;1(7590):323–326. doi: 10.1016/s0140-6736(69)91294-x. [DOI] [PubMed] [Google Scholar]
  9. Cornet A., Dubrisay J., Godeau P., Duboys Y., Rioux C., Blanc D., Gaux J. C., Sicard D. Maladie thrombosante au cours d'un syndrome lupique révélé par un oestroprogestatif. Ann Med Interne (Paris) 1971 Nov;122(11):1151–1154. [PubMed] [Google Scholar]
  10. Cuatrecasas P. Protein purification by affinity chromatography. Derivatizations of agarose and polyacrylamide beads. J Biol Chem. 1970 Jun;245(12):3059–3065. [PubMed] [Google Scholar]
  11. DuBois E. L., Strain L., Ehn M., Bernstein G., Friou G. J. L.E. cells after oral contraceptives. Lancet. 1968 Sep 21;2(7569):679–679. doi: 10.1016/s0140-6736(68)92528-2. [DOI] [PubMed] [Google Scholar]
  12. GRABAR P., WILLIAMS C. A., Jr Méthode immuno-électrophorétique d'analyse de mélanges de substances antigéniques. Biochim Biophys Acta. 1955 May;17(1):67–74. doi: 10.1016/0006-3002(55)90320-6. [DOI] [PubMed] [Google Scholar]
  13. Godefroi V. C., Brooks S. C. Improved gel-filtration method for analysis of estrogen receptor binding. Anal Biochem. 1973 Feb;51(2):335–344. doi: 10.1016/0003-2697(73)90486-7. [DOI] [PubMed] [Google Scholar]
  14. Hoyumpa A. M., Jr, Schiff L., Helfman E. L. Budd-Chiari syndrome in women taking oral contraceptives. Am J Med. 1971 Jan;50(1):137–140. doi: 10.1016/0002-9343(71)90213-0. [DOI] [PubMed] [Google Scholar]
  15. Kahn D., Andrieu J. M., Dray F. Evaluation of some binding parameters of hapten-antibody complexes using dextran-coated charcoal to separate the bound and free fractions. Immunochemistry. 1974 Jul;11(7):327–332. doi: 10.1016/0019-2791(74)90183-9. [DOI] [PubMed] [Google Scholar]
  16. Kirkegaard L., Agee C. C. Intervent dilution chromatography: concept for separation of strongly interacting macromolecules. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2424–2428. doi: 10.1073/pnas.70.8.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Matz M. H. Erythema nodosum and contraceptive medication. N Engl J Med. 1967 Feb 9;276(6):351–352. doi: 10.1056/NEJM196702092760620. [DOI] [PubMed] [Google Scholar]
  19. Pearlman W. H., Fong I. F. Steroid binding properties of some peptide fragments of bovine serum albumin obtained on peptic digestion. J Biol Chem. 1972 Dec 25;247(24):8078–8084. [PubMed] [Google Scholar]
  20. Raynaud J. P., Mercier-Bodard C., Baulieu E. E. Rat estradiol binding plasma protein (EBP). Steroids. 1971 Dec;18(6):767–788. doi: 10.1016/0039-128x(71)90035-3. [DOI] [PubMed] [Google Scholar]
  21. Rothwell-Jackson R. L. Budd-Chiari syndrome after oral contraceptives. Br Med J. 1968 Jan 27;1(5586):252–252. doi: 10.1136/bmj.1.5586.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sartwell P. E., Masi A. T., Arthes F. G., Greene G. R., Smith H. E. Thromboembolism and oral contraceptives: an epidemiologic case-control study. Am J Epidemiol. 1969 Nov;90(5):365–380. doi: 10.1093/oxfordjournals.aje.a121082. [DOI] [PubMed] [Google Scholar]
  23. Seligmann M., Brouet J. C. Antibody activity of human myeloma globulins. Semin Hematol. 1973 Apr;10(2):163–177. [PubMed] [Google Scholar]
  24. Vessey M. P., Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J. 1968 Apr 27;2(5599):199–205. doi: 10.1136/bmj.2.5599.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  26. Wynne-Roberts C. R. The evaluation of hydrocortisone antibodies produced in rabbits and sheep. I. Radioimmunoassay. Immunology. 1974 Jan;26(1):97–113. [PMC free article] [PubMed] [Google Scholar]
  27. de Gennes J. L., Turpin G., Truffert J. Accidents vasculaires majeurs en cours de traitment contraceptif oral, et découverte rétrospective d'une hyperlipidémie idiopathique. A propos de 9 observations. Presse Med. 1970 Mar 7;78(12):541–546. [PubMed] [Google Scholar]

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