Abstract
In vitro anti-acetylcholine receptor antibody (anti-AChR Ab) production by peripheral blood lymphocytes (PBL) and thymic lymphocytes was investigated in 52 patients with myasthenia gravis (MG). There was a positive correlation betweenin vitro anti-AChR Ab synthesis andin vivo titers. A relationship between the rates of synthesis by PBL and histological abnormalities of the thymus was also observed. Patients with hyperplastic thymus tended to produce the largest amountsin vitro, while those with an involuted thymus produced little or none. Production in thymoma patients is likely to correlate with the histological nature of the thymus associated with the tumor.In vitro Ab synthesis was modulated by the depletion of a cell subset for half of the patients tested. Finally, anti-AChR Ab production by thymocytes but not by PBL is enhanced by the addition of autologous or allogeneic thymic epithelial cells, suggesting a possible role of thymic epithelial cells in the autosensitization against AChR occurring in the thymus.
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Lindstrom JM, Seybold ME, Lennon, VA, Whittingham S: Antibody to acetylcholine receptor in myasthenia gravis: Prevalence, clinical correlates and diagnostic value. Neurology (Minn) 26:1054–1059, 1976
Vincent A, Scadding GK, Thomas HC, Newsom-Davis J: In vitro synthesis of anti-acetylcholine receptor antibody by thymic lymphocytes in myasthenia gravis. Lancet 1:305–307, 1978
Newsom-Davis J, Willcox N, Calder L: Thymus cells in myasthenia gravis selectively enhance production of antiacetylcholine receptor antibody by autologous blood lymphocytes. N Engl J Med 305:1313–1318, 1981
Richman DP, Patrick J, Arnason GW: Cellular immunity in myasthenia gravis. Response to purified acetylcholine receptor and autologous thymocytes. N Engl J Med 294:694–698, 1976
Lepage V, Berrih S, Morel E, Real O, Degos L: HLA and myasthenia gravis: A new association. Disease Markers 1:181–187, 1983
Berrih S, Morel E, Gaud C, Raimond F, Le Brigand H, Bach JF: Anti-AChR antibodies thymic histology, and T cell subsets in myasthenia gravis. Neurology (Cleveland) 34:66–71, 1984
Shinomiya N, Yata J: B and T cell involvement in antiacetylcholine receptor antibody formation in myasthenia gravis. Clin Exp Immunol 46:277–285, 1981
Castelman B: The pathology of the thymus gland in myasthenia gravis. Ann NY Acad Sci 135:496–505, 1966
Scadding GK, Vincent A, Newsom-Davis J, Henry K: Acetylcholine receptor antibody synthesis by thymic lymphocytes: Correlation with thymic histology. Neurology (NY) 31:935–943, 1981
Fuchs S, Schmidt-Hopfeld I, Tridente G, Tarrab-Hazdai R: Thymic lymphocytes bear a surface antigen which cross-reacts with acetylcholine receptor. Nature 287:162–164, 1980
Engel WK, Trotter JL, McFarlin DE, McIntosh CL: Thymic epithelial cell contains acetylcholine receptor. Lancet 1:1310–1311, 1977
Stutman O: Intrathymic and extrathymic T cell maturation. Immunol Rev 42:138, 1978
Bach JF, Papiernik M: Cellular and molecular signals in T cell differentiation.In Microenvironment in Haemopoietic and Lymphoid Differentiation, Ciba Foundation Symposium 84. Pittman, London, 1981, pp 230–235
Berrih-Aknin S, Morel E, Raimond F, Safar D, Gaud C, Binet JP, Levasseur P, Bach JF: The role of the thymus in myasthenia gravis. Immunohistological and immunological studies in 115 cases. Ann NY Acad Sci (in press)
Levine GD, Rosai J: Thymic hyperplasia and neoplasia. A review of current concepts. Prog Hum Pathol 9:495–515, 1978
Berrih S, Gaud C, Bach MA, Le Brigand JP, Binet JP, Bach JF: Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies. Clin Exp Immunol 45:1–8, 1981
Vernet der Garabedian B, Morel E, Bach JF: Heterogeneity of antibodies directed against the α-bungarotoxin binding site on human acetylcholine receptor and severity of myasthenia gravis. J Neuroimmunol 12:65–74, 1986
Berrih S, Savino W, Azoulay M, Dardenne M, Bach JF: Production of anti-thymulin (FTS) monoclonal antibodies by immunization against human thymic epithelial cells. J Histochem Cytochem 32:432–438, 1984
Willcox HNA, Newsom-Davis J, Calder LR: Cell types required for anti-acetylcholine receptor antibody synthesis by cultured thymocytes and blood lymphocytes in myasthenia gravis. Clin Exp Immunol 58:97–106, 1984
Vincent A, Scadding GK, Clarke C, Newsom-Davis J: Anti-acetylcholine receptor antibody synthesis in culture.In Plasmapheresis and the Immunobiology of Myasthenia Gravis, P Dau (ed). Boston, Houghton Mifflin, 1979, pp 59–71
Miller AE, Hudson J, Tindall RSA: Immune regulation in myasthenia gravis: Evidence for an increased suppressor T-cell population. Ann Neurol 12:341–347, 1982
Harfast B, Huddlestone JR, Braheny S, Seybold ME, Oldstone MBA: Myasthenia gravis: In vitro immunoglobulin production with pokeweed mitogen challenge and B- and T-lymphocyte competence. Clin Immunol Immunopathol 20:336–345, 1981
Tindall RSA, Miller A, Smith TV: Humoral immunity in myasthenia gravis: Defect in immunoregulation? Neurology 31:85–88, 1981
Shinomiya N, Yata J, Sasazuki T: T-cell subsets regulating anti-acetylcholine-receptor-antibody formation in myasthenia gravis and characterization of suppressor T-cell factors involved. Clin Immunol Immunopathol 33:182–190, 1984
Lisak RP, Laramore C, Levinson AI, Zweiman B, Moskovits AR: Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor. Ann Neurol 19:87–89, 1986
Jones BM: B cell activation by pokeweed mitogen in cultures of normal peripheral blood lymphocytes depleted of T regulator subsets by treatment with OKT4 and OKT8 monoclonal antibodies. Clin Exp Immunol 51:461–469, 1983
Thomas Y, Rogozinski L, Irigoyen OH, Friedman SM, Kung PC, Goldstein G, Chess L: Functional analysis of human T cell subsets defined by monoclonal antibodies. J Exp Med 154:459–467, 1981
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 NY Acad Sci 377:393–402, 1981
McLachlan SM, Nicholson LVB, Venables G, Mastalgia FL, Bates D, Smith BR, Hall R: Acetylcholine receptor antibody synthesis in lymphocyte cultures. J Clin Lab Immunol 5:137–142, 1981
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 (Cleveland) 34:1182–1186, 1984
Berrih S, Arenzana-Seisdedos F, Cohen S, Devos R, Charron D, Virelizier JL: Interferon-γ modulates HLA class II antigen expression on cultured human thymic epithelial cells. J Immunol 135:1165–1171, 1985
McLachlan SM, Dickinson AM, Malcolm A, Farndon JR, Young E, Proctor SJ, Smith BR: Thyroid autoantibody synthesis by cultures of thyroid and peripheral blood lymphocytes. I. Lymphocyte markers and response to pokeweed mitogen. Clin Exp Immunol 52:45–53, 1983
Berrih S, Safar D, Levasseur P, Gaud C, Bach JF: The in vivo effects of corticosteroids on thymocyte subsets in myasthenia gravis. J Clin Immunol 4:92–97, 1984
Berrih S, Savino W, Cohen S: Extracellular matrix of the human thymus: Immunofluorescence studies on frozen sections and cultured epithelial cells. J Histochem Cytochem 33:655–664, 1985
Staber FG, Fink U, Sack W: B lymphocytes in the thymus of patients with myasthenia gravis. N Engl J Med 292:1032–1033, 1975
Perlo VP, Poskanzer DC, Schwab RS, Viets HR, Osserman KE, Genkins G: Myasthenia gravis: Evaluation of treatment in 1 355 patients. Neurology (Minn) 16:431–439, 1966
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Safar, D., Berrih-Aknin, S. & Morel, E. In vitro anti-acetylcholine receptor antibody synthesis by myasthenia gravis patient lymphocytes: Correlations with thymic histology and thymic epithelial-cell interactions. J Clin Immunol 7, 225–234 (1987). https://doi.org/10.1007/BF00915728
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DOI: https://doi.org/10.1007/BF00915728