Abstract
The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abramsky O., Brenner T. Alpha-fetoprotein inhibits antibody binding to acetylcholine receptor. Significance for myasthenia gravis and other autoimmune diseases. Isr J Med Sci. 1979 Nov;15(11):943–945. [PubMed] [Google Scholar]
- Abramsky O., Brenner T., Lisak R. P., Zeidman A., Beyth Y. Significance in neonatal myasthenia gravis of inhibitory effect of amniotic fluid on binding of antibodies to acetylcholine receptor. Lancet. 1979 Dec 22;2(8156-8157):1333–1335. doi: 10.1016/s0140-6736(79)92815-0. [DOI] [PubMed] [Google Scholar]
- Adcock E. W., 3rd, Teasdale T., August C. S., Cox S., Meschia G., Ballaglia T. C., Naughton M. A. Human chorionic gonadotropin: its possible role in maternal lymphocyte suppression. Science. 1973 Aug 31;181(4102):845–847. doi: 10.1126/science.181.4102.845. [DOI] [PubMed] [Google Scholar]
- Aharonov A., Abramsky O., Tarrab-Hazdai R., Fuchs S. Humoral antibodies to acetylcholine receptor in patients with myasthenia gravis. Lancet. 1975 Aug 23;2(7930):340–342. doi: 10.1016/s0140-6736(75)92779-8. [DOI] [PubMed] [Google Scholar]
- Aharonov A., Tarrab-Hazdai R., Silman I., Fuchs S. Immunochemical studies on acetylcholine receptor from Torpedo californica. Immunochemistry. 1977 Feb;14(2):129–137. doi: 10.1016/0019-2791(77)90291-9. [DOI] [PubMed] [Google Scholar]
- Appel S. H., Almon R. R., Levy N. Acetylcholine receptor antibodies in myasthenia gravis. N Engl J Med. 1975 Oct 9;293(15):760–761. doi: 10.1056/NEJM197510092931508. [DOI] [PubMed] [Google Scholar]
- Auer I. O., Kress H. G. Suppression of the primary cell-mediated immune response by human alpha1-fetoprotein in vitro. Cell Immunol. 1977 Apr;30(1):173–179. doi: 10.1016/0008-8749(77)90058-2. [DOI] [PubMed] [Google Scholar]
- BARSI I. A new treatment of rheumatoid arthritis. Br Med J. 1947 Aug 16;2(4519):252–252. doi: 10.1136/bmj.2.4519.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bender A. N., Ringel S. P., Engel W. K., Daniels M. P., Vogel Z. Myasthenia gravis: a serum factor blocking acetylcholine receptors of the human neuromuscular junction. Lancet. 1975 Mar 15;1(7907):607–609. doi: 10.1016/s0140-6736(75)91886-3. [DOI] [PubMed] [Google Scholar]
- Brenner T., Abramsky O., Lisak R. P., Zweiman B., Tarrab-Hazdai R., Fuchs S. Radioimmunoassay of antibodies to acetylcholine receptor in serum of myasthenia gravis patients. Isr J Med Sci. 1978 Sep;14(9):986–989. [PubMed] [Google Scholar]
- Chambers D. C., Hall J. E., Boyce J. Myasthenia gravis and pregnancy. Obstet Gynecol. 1967 Apr;29(4):597–603. [PubMed] [Google Scholar]
- Dattwyler R. J., Murgita R. A., Tomasi T. B., Jr Binding of alpha-foetoprotein to murine T cells. Nature. 1975 Aug 21;256(5519):656–657. doi: 10.1038/256656a0. [DOI] [PubMed] [Google Scholar]
- Dattwyler R. J., Tomasi T. B. Inhibition of sensitization of T-cells by alpha-fetoprotein. Int J Cancer. 1975 Dec 15;16(6):942–945. doi: 10.1002/ijc.2910160608. [DOI] [PubMed] [Google Scholar]
- Drachman D. B. Myasthenia gravis (first of two parts). N Engl J Med. 1978 Jan 19;298(3):136–142. doi: 10.1056/NEJM197801192980305. [DOI] [PubMed] [Google Scholar]
- Fenichel G. M. Clinical syndromes of myasthenia in infancy and childhood. A review. Arch Neurol. 1978 Feb;35(2):97–103. doi: 10.1001/archneur.1978.00500260035009. [DOI] [PubMed] [Google Scholar]
- Fraser D., Turner J. W. Myasthenia Gravis and Pregnancy. Proc R Soc Med. 1963 May;56(5):379–381. doi: 10.1177/003591576305600523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOULD I. D. Rheumatoid arthritis aggravated by pregnancy and controlled by cortisone. N Y State J Med. 1955 Apr 15;55(8):1164–1166. [PubMed] [Google Scholar]
- Hay D. M. Myasthenia gravis and pregnancy. J Obstet Gynaecol Br Commonw. 1969 Apr;76(4):323–329. doi: 10.1111/j.1471-0528.1969.tb05840.x. [DOI] [PubMed] [Google Scholar]
- Hill C. A., Finn R., Denye V. Depression of cellular immunity in pregnancy due to a serum factor. Br Med J. 1973 Sep 8;3(5879):513–514. doi: 10.1136/bmj.3.5879.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsu C. C. Peripheral blood lymphocyte responses to phytohemagglutinin and pokeweed mitogen during pregnancy. Proc Soc Exp Biol Med. 1974 Jul;146(3):771–775. doi: 10.3181/00379727-146-38190. [DOI] [PubMed] [Google Scholar]
- JOSEPHS C. Observations on the treatment of rheumatoid arthritis by transfusions of blood from pregnant women. Br Med J. 1954 Jul 17;2(4880):134–135. doi: 10.1136/bmj.2.4880.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KAPLAN D., DIAMOND H. RHEUMATOID ARTHRITIS AND PREGNANCY. Clin Obstet Gynecol. 1965 Jun;17:286–303. doi: 10.1097/00003081-196506000-00004. [DOI] [PubMed] [Google Scholar]
- KEYNES G. Obstetrics and gynaecology in relation to thyrotoxicosis and myasthenia gravis. J Obstet Gynaecol Br Emp. 1952 Apr;59(2):173–182. doi: 10.1111/j.1471-0528.1952.tb04112.x. [DOI] [PubMed] [Google Scholar]
- Kasakura S. A factor in maternal plasma during pregnancy that suppresses the reactivity of mixed leukocyte cultures. J Immunol. 1971 Nov;107(5):1296–1301. [PubMed] [Google Scholar]
- Kaye M. D., Jones W. R., Ing R. M. Studies of a possible immunosuppressive action of human chorionic gonadotrophin. J Reprod Fertil. 1972 Jan;28(1):165–165. doi: 10.1530/jrf.0.0280165. [DOI] [PubMed] [Google Scholar]
- Keesey J., Lindstrom J., Cokely H. Anti-acetylcholine receptor antibody in neonatal myasthenia gravis. N Engl J Med. 1977 Jan 6;296(1):55–55. doi: 10.1056/NEJM197701062960125. [DOI] [PubMed] [Google Scholar]
- Lau H. L., Linkins S. E. Alpha-fetoprotein. Am J Obstet Gynecol. 1976 Mar 1;124(5):533–554. doi: 10.1016/0002-9378(76)90184-8. [DOI] [PubMed] [Google Scholar]
- Leikin S. Depressed maternal lymphocyte response to phytohaemagglutinin in pregnancy. Lancet. 1972 Jul 1;2(7766):43–43. doi: 10.1016/s0140-6736(72)91300-1. [DOI] [PubMed] [Google Scholar]
- Lester E. P., Miller J. B., Baron J. M., Yachnin S. Inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP): studies on the mode of HAFP action and the role of HAFP polymorphism. Immunology. 1978 Feb;34(2):189–198. [PMC free article] [PubMed] [Google Scholar]
- Lindstrom J. M., Engel A. G., Seybold M. E., Lennon V. A., Lambert E. H. Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. J Exp Med. 1976 Sep 1;144(3):739–753. doi: 10.1084/jem.144.3.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindstrom J. M., Seybold M. E., Lennon V. A., Whittingham S., Duane D. D. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 1976 Nov;26(11):1054–1059. doi: 10.1212/wnl.26.11.1054. [DOI] [PubMed] [Google Scholar]
- Mittag T., Kornfeld P., Tormay A., Woo C. Detection of anti-acetylcholine receptor factors in serum and thymus from patients with myasthenia gravis. N Engl J Med. 1976 Mar 25;294(13):691–694. doi: 10.1056/NEJM197603252941303. [DOI] [PubMed] [Google Scholar]
- Monnier V. M., Fulpius B. W. A radioimmunoassay for the quantitative evaluation of anti-human acetylcholine receptor antibodies in myasthenia gravis. Clin Exp Immunol. 1977 Jul;29(1):16–22. [PMC free article] [PubMed] [Google Scholar]
- Murgita R. A., Goidl E. A., Kontianen S., Wigzell H. alpha-Fetoprotein induces suppressor T cells in vitro. Nature. 1977 May 19;267(5608):257–259. doi: 10.1038/267257a0. [DOI] [PubMed] [Google Scholar]
- Murgita R. A. The immunosuppressive role of alpha-fetoprotein during pregnancy. Scand J Immunol. 1976;5(9):1003–1014. doi: 10.1111/j.1365-3083.1976.tb03052.x. [DOI] [PubMed] [Google Scholar]
- Murgita R. A., Tomasi T. B., Jr Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response. J Exp Med. 1975 Feb 1;141(2):269–286. doi: 10.1084/jem.141.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murgita R. A., Wigzell H. The effects of mouse alpha-fetoprotein on T-cell-dependent and T-cell-independent immune responses in vitro. Scand J Immunol. 1976;5(10):1215–1220. doi: 10.1111/j.1365-3083.1976.tb00265.x. [DOI] [PubMed] [Google Scholar]
- Namba T., Brown S. B., Grob D. Neonatal myasthenia gravis: report of two cases and review of the literature. Pediatrics. 1970 Mar;45(3):488–504. [PubMed] [Google Scholar]
- Ogra S. S., Murgita R. A., Tomasi T. B., Jr Immunosuppressive activity of mouse amniotic fluid. Immunol Commun. 1974;3(5):497–508. doi: 10.3109/08820137409061129. [DOI] [PubMed] [Google Scholar]
- PLAUCHE W. C. MYASTHENIA GRAVIS IN PREGNANCY. Am J Obstet Gynecol. 1964 Feb 1;88:404–409. [PubMed] [Google Scholar]
- Persellin R. H., Thoi L. L. Human polymorphonuclear leukocyte phagocytosis in pregnancy. Development of inhibition during gestation and recovery in the postpartum period. Am J Obstet Gynecol. 1979 Jun 1;134(3):250–255. doi: 10.1016/s0002-9378(16)33028-9. [DOI] [PubMed] [Google Scholar]
- Ruoslahti E., Seppälä M. -Foetoprotein in normal human serum. Nature. 1972 Jan 21;235(5334):161–162. doi: 10.1038/235161a0. [DOI] [PubMed] [Google Scholar]
- Schiff R. I., Mercier D., Buckley R. H. Inability of gestational hormones to account for the inhibitory effects of pregnancy plasmas on lymphocyte responses in vitro. Cell Immunol. 1975 Nov;20(1):69–80. doi: 10.1016/0008-8749(75)90085-4. [DOI] [PubMed] [Google Scholar]
- Shutt D. A., Smith I. D., Shearman R. P. Oestrone, oestradiol-17beta and oestriol levels in human foetal plasma during gestation and at term. J Endocrinol. 1974 Feb;60(2):333–341. doi: 10.1677/joe.0.0600333. [DOI] [PubMed] [Google Scholar]
- Tormey D. C., Fudenberg H. H., Kamin R. M. Effect of prednisolone on synthesis of DNA and RNA by human lymphocytes in vitro. Nature. 1967 Jan 21;213(5073):281–282. doi: 10.1038/213281a0. [DOI] [PubMed] [Google Scholar]
- Walker J. S., Freeman C. B., Harris R. Lymphocyte reactivity in pregnancy. Br Med J. 1972 Aug 19;3(5824):469–469. doi: 10.1136/bmj.3.5824.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yachnin S. Demonstration of the inhibitory effect of human alpha-fetoprotein on in vitro transformation of human lymphocytes. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2857–2861. doi: 10.1073/pnas.73.8.2857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yachnin S., Lester E. Inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP); comparison of foetal and hepatoma HAFP and kinetic studies in vitro immunosuppression. Clin Exp Immunol. 1976 Dec;26(3):484–490. [PMC free article] [PubMed] [Google Scholar]
