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. 1992 Feb;87(2):246–250. doi: 10.1111/j.1365-2249.1992.tb02982.x

Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy.

J B Kuks 1, P C Limburg 1, H J Oosterhuis 1, T H The 1
PMCID: PMC1554251  PMID: 1735188

Abstract

Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.

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Selected References

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  1. Benner R., Hijmans W., Haaijman J. J. The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. Clin Exp Immunol. 1981 Oct;46(1):1–8. [PMC free article] [PubMed] [Google Scholar]
  2. Berrih S., Le Brigand H., Levasseur P., Gaud C., Bach J. F. Depletion of helper/inducer T cells after thymectomy in myasthenic patients. Clin Immunol Immunopathol. 1983 Aug;28(2):272–281. doi: 10.1016/0090-1229(83)90161-7. [DOI] [PubMed] [Google Scholar]
  3. Clement L. T., Dagg M. K., Gartland G. L. Small, resting B cells can be induced to proliferate by direct signals from activated helper T cells. J Immunol. 1984 Feb;132(2):740–744. [PubMed] [Google Scholar]
  4. Conti-Tronconi B. M., Scotti A., Sghirlanzoni A., Clementi F. Specific involvement of peripheral T lymphocytes against acetylcholine receptors in myasthenia gravis. J Neurol Neurosurg Psychiatry. 1983 Sep;46(9):832–836. doi: 10.1136/jnnp.46.9.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cox A., Lisak R. P., Skolnik P., Zweiman B. Effect of thymectomy on blood T-cell subsets in myasthenia gravis. Ann Neurol. 1986 Mar;19(3):297–298. doi: 10.1002/ana.410190314. [DOI] [PubMed] [Google Scholar]
  6. Dalakas M. C., Rose J. W., Paul J., Engel W. K., McClure J. E., Goldstein A. L. Increased circulation of T lymphocytes bearing surface thymosin alpha 1 in patients with myasthenia gravis: effect of thymectomy. Neurology. 1983 Feb;33(2):144–149. doi: 10.1212/wnl.33.2.144. [DOI] [PubMed] [Google Scholar]
  7. Fujii Y., Monden Y., Nakahara K., Hashimoto J., Kawashima Y. Antibody to acetylcholine receptor in myasthenia gravis: production by lymphocytes from thymus or thymoma. Neurology. 1984 Sep;34(9):1182–1186. doi: 10.1212/wnl.34.9.1182. [DOI] [PubMed] [Google Scholar]
  8. Hohlfeld R., Toyka K. V., Heininger K., Grosse-Wilde H., Kalies I. Autoimmune human T lymphocytes specific for acetylcholine receptor. Nature. 1984 Jul 19;310(5974):244–246. doi: 10.1038/310244a0. [DOI] [PubMed] [Google Scholar]
  9. Keightley R. G., Cooper M. D., Lawton A. R. The T cell dependence of B cell differentiation induced by pokeweed mitogen. J Immunol. 1976 Nov;117(5 Pt 1):1538–1544. [PubMed] [Google Scholar]
  10. Kelley R. E., Keesey J. C., Goymerac V., Larrick S. B., Kebo D., Buffkin D. Immunoregulation of total IgC synthesis in myasthenia gravis. Ann N Y Acad Sci. 1981;377:403–410. doi: 10.1111/j.1749-6632.1981.tb33748.x. [DOI] [PubMed] [Google Scholar]
  11. Kuks J. B., Oosterhuis H. J., Limburg P. C., The T. H. Anti-acetylcholine receptor antibodies decrease after thymectomy in patients with myasthenia gravis. Clinical correlations. J Autoimmun. 1991 Apr;4(2):197–211. doi: 10.1016/0896-8411(91)90018-8. [DOI] [PubMed] [Google Scholar]
  12. Levinson A. I., Zweiman B., Lisak R. P., Dziarski A., Moskovitz A. R. Thymic B-cell activation in myasthenia gravis. Neurology. 1984 Apr;34(4):462–468. doi: 10.1212/wnl.34.4.462. [DOI] [PubMed] [Google Scholar]
  13. Limburg P. C., Hummel-Tappel E., Oosterhuis H. J., The T. H. In vitro T-cell dependent B-cell activity in myasthenia gravis. Clin Exp Immunol. 1985 Jul;61(1):31–38. [PMC free article] [PubMed] [Google Scholar]
  14. Lisak R. P., Laramore C., Levinson A. I., Zweiman B., Moskovitz A. R., Witte A. In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood cells: role of suppressor T cells in normal subjects. Neurology. 1984 Jun;34(6):802–805. doi: 10.1212/wnl.34.6.802. [DOI] [PubMed] [Google Scholar]
  15. Lisak R. P., Levinson A. I., Zweiman B., Kornstein M. J. In vitro synthesis of IgG and antibodies to AChR by peripheral and thymic lymphocytes. Ann N Y Acad Sci. 1987;505:39–49. doi: 10.1111/j.1749-6632.1987.tb51281.x. [DOI] [PubMed] [Google Scholar]
  16. Matsui M., Fukuyama H., Akiguchi I., Kameyama M. Circulating CD4+CD8+ cells in myasthenia gravis: supplementary immunological parameter for long-term prognosis. J Neurol. 1989 Sep;236(6):329–335. doi: 10.1007/BF00314374. [DOI] [PubMed] [Google Scholar]
  17. Melms A., Schalke B. C., Kirchner T., Müller-Hermelink H. K., Albert E., Wekerle H. Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients. J Clin Invest. 1988 Mar;81(3):902–908. doi: 10.1172/JCI113401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Newsom-Davis J., Willcox N., Scadding G., Calder L., Vincent A. Anti-acetylcholine receptor antibody synthesis by cultured lymphocytes in myasthenia gravis: thymic and peripheral blood cell interactions. Ann N Y Acad Sci. 1981;377:393–402. doi: 10.1111/j.1749-6632.1981.tb33747.x. [DOI] [PubMed] [Google Scholar]
  19. Newsom-Davis J., Willcox N., Schluep M., Harcourt G., Vincent A., Mossman S., Wray D., Burges J. Immunological heterogeneity and cellular mechanisms in myasthenia gravis. Ann N Y Acad Sci. 1987;505:12–26. doi: 10.1111/j.1749-6632.1987.tb51279.x. [DOI] [PubMed] [Google Scholar]
  20. Scadding G. K., Webster A. D., Ross M., Thomas H. C., Havard C. W. Humoral immunity before and after thymectomy in myasthenia gravis. Neurology. 1979 Apr;29(4):502–506. doi: 10.1212/wnl.29.4.502. [DOI] [PubMed] [Google Scholar]
  21. Schalke B. C., Klinkert W. E., Wekerle H., Dwyer D. S. Enhanced activation of a T cell line specific for acetylcholine receptor (AChR) by using anti-AChR monoclonal antibodies plus receptors. J Immunol. 1985 Jun;134(6):3643–3648. [PubMed] [Google Scholar]
  22. Sommer N., Willcox N., Harcourt G. C., Newsom-Davis J. Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. Ann Neurol. 1990 Sep;28(3):312–319. doi: 10.1002/ana.410280303. [DOI] [PubMed] [Google Scholar]
  23. Swain S. L., Dutton R. W. Consequences of the direct interaction of helper T cells with B cells presenting antigen. Immunol Rev. 1987 Oct;99:263–280. doi: 10.1111/j.1600-065x.1987.tb01180.x. [DOI] [PubMed] [Google Scholar]
  24. Tronconi B. C., Morgutti M., Cornelio F., Clementi F. Effect of thymectomy on cellular immunity in myasthenia gravis. Lancet. 1978 Jan 7;1(8054):46–47. doi: 10.1016/s0140-6736(78)90395-1. [DOI] [PubMed] [Google Scholar]
  25. Van de Griend R. J., Carreno M., Van Doorn R., Leupers C. J., Van den Ende A., Wijermans P., Oosterhuis H. J., Astaldi A. Changes in human T lymphocytes after thymectomy and during senescence. J Clin Immunol. 1982 Oct;2(4):289–295. doi: 10.1007/BF00915069. [DOI] [PubMed] [Google Scholar]
  26. Wijermans P., Oosterhuis H. J., Astaldi G. C., Schellekens P. T., Astaldi A. Influence of adult thymectomy on immunocompetence in patients with myasthenia gravis. J Immunol. 1980 Apr;124(4):1977–1982. [PubMed] [Google Scholar]
  27. Willcox H. N., Newsom-Davis J., Calder L. R. Cell types required for anti-acetylcholine receptor antibody synthesis by cultured thymocytes and blood lymphocytes in myasthenia gravis. Clin Exp Immunol. 1984 Oct;58(1):97–106. [PMC free article] [PubMed] [Google Scholar]
  28. Wolf R. E., Goldstein A. L., Ziff M. Suppression by thymosin of pokeweed mitogen-induced differentiation of human B cells. Clin Immunol Immunopathol. 1978 Nov;11(3):303–306. doi: 10.1016/0090-1229(78)90054-5. [DOI] [PubMed] [Google Scholar]

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