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Heterogenität von Acetylcholinrezeptor-Antikörpern bei Myasthenia gravis Patienten

Heterogenity of acetylcholin-receptor-antibodies in myasthenia gravis

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Summary

Antibodies against the nicotinic acetylcholine receptor in sera of 21 myasthenia gravis patients were checked for their ability to block or split binding of α-bungarotoxin to the human acetylcholine receptor. Affinity-purified acetylcholine receptors from human skeletal muscle were used in parallel in the common precipitation assay and an inhibition assay. Cross-reactivity of acetylcholine receptor antibodies was analyzed with receptor preparation from different species (calf, rat,Torpedo c. andElectrophorus e.), purified identically to high specific activity. An antibody pattern was set up for each patient and related to the clinical state of the disease.

α-Bungarotoxin-inhibiting antibodies were demonstrable in 74% of myasthenia gravis patients, α-bgt displacing antibodies were found in 39% of the investigated sera. Broad cross-reactivity with acetylcholine receptors from other mammalian muscle was evident (calf 75%, rat 90%) only very few sera reacted with acetylcholine receptors from electric fish (Torpedo c. 14%,Electrophorus e. 38%). Antibody concentrations determined by using xenoantigens were much lower than those obtained by human acetylcholine receptor.

The lack of a clear-cut correlation between the amount of serum antibodies and the clinical state of myasthenia gravis can be explained by the established antibody-heterogeneity, shown by a constant antibody pattern characteristic for each patient. However, between this specific antibody pattern and the state of the disease no correlation could be established either.

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Literatur

  1. Almon RR, Andrew CG, Appel SH (1974) Serum globulin in Myasthenia gravis: inhibition of α-bungarotoxin binding to acetylcholine receptors. Science 186:55–57

    Google Scholar 

  2. Barkas T, McPhail Gairns J, Jackson Kerr H, Coggins JR, Simpson JA (1982) α-Bungarotoxin binding to the nicotinic acetylcholine receptor is inhibited by two distinct subpopulations of anti-receptor antibodies. Eur J Immunol 12:757–761

    Google Scholar 

  3. Barkas T, Simpson JA (1982) α-Bungarotoxin displacing antibody in myasthenia gravis. J Clin Lab Immunol 9:113–117

    Google Scholar 

  4. Barkas T, Simpson JA (1982) Lack of inter-animal cross-reaction of anti-acetylcholine receptor antibodies at the receptor-binding site as demonstrated by heterologous anti-idiotype antisera: implications for immunotherapy of myasthenia gravis. Clin Exp Immunol 47:119–126

    Google Scholar 

  5. DeCrousaz G, Fulpius B, Monnier V, Regli F (1978) Dosage des anticorps dirigés contre le récepteur nicotinique de l'acétylcholine: corrélations clinico-immunologiques chez 30 myasthéniques. Schweiz Med Wochenschr 108:602–607

    Google Scholar 

  6. Drachman DB, Adams RN, Josifek LF, Self SG (1982) Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of Myasthenia gravis. N Engl J Med 307:769–775

    Google Scholar 

  7. Druschky KF, Stadler HW, Daun H (1981) Thorakale Computertomographie bei Myasthenia gravis zur Beurteilung des Thymus. Fortschr Neurol Psychiat 49:415–421

    Google Scholar 

  8. Dwyer DS, Kearney JF, Bradley RJ, Kemp GE, Oh SJ (1981) Interaction of human antibody and murine monoclonal antibody with muscle acetylcholine receptor. Ann NY Acad Sci 377:143–157

    Google Scholar 

  9. Fischbach M, Lindstrom J, Talal N (1981) Antibodies to polyadenylic acid in patients with myasthenia gravis. Clin Exp Immunol 43:73–79

    Google Scholar 

  10. Garlepp MJH, Kay PH, Dawkins RL, Bucknall RC, Kemp A (1981) Cross-reactivity of anti-acetylcholine receptor auto-antibodies. Muscle Nerve 4:282–288

    Google Scholar 

  11. Gotti C, Conti-Tronconi BM, Raftery MA (1982) Mammalian muscle acetylcholine receptor purification and characterisation. Biochemistry 21:3148–3154

    Google Scholar 

  12. James RW, Kato AC, Rey MJ, Fulpius BW (1980) Monoclonal antibodies directed against the neurotransmitter binding site of nicotinic acetylcholine receptor. FEBS Lett 120:145–148

    Google Scholar 

  13. Kalies I, Kalden JR, Heinz F, Janzen RWCh, Lachenmayer L (1979) Nachweis von Acetylcholin-Rezeptor Antikörpern im Serum von Myasthenia gravis Patienten unter Verwendung affinitätschromatographisch gereinigter humaner Acetylcholin-Rezeptor-Präparationen. Klin Wochenschr 57:875–881

    Google Scholar 

  14. Kalies I, Heinz F, Hohlfeld R, Wekerle H, Birnberger KL, Kalden JR (1983) Biochemical and immunological properties of acetylcholine receptors from human muscle. Molec Cell Biochem (submitted)

  15. Kalden JR (1970) Die Pathogenese der Myasthenia gravis als immunologisches Problem. Klin Wochenschr 48:4–13

    Google Scholar 

  16. Lefvert AK, Bergstrom K, Matell G, Osterman PO, Pirskanen R (1978) Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications. J Neurol Neurosurg Psychiatry 41:394–403

    Google Scholar 

  17. Lennon VA, Lambert EH (1980) Myasthenia gravis induced by monoclonal antibodies to acetylcholine receptors. Nature 285:238–240

    Google Scholar 

  18. Lindstrom J (1977) An assay for antibodies to human acetylcholine receptor in serum from patients with Myasthenia gravis. Clin Immunol Immunopathol 7:36–43

    Google Scholar 

  19. Lindstrom J, Campbell M, Nave B (1978) Specificities of antibodies to acetylcholine receptors. Muscle Nerve 1:140–145

    Google Scholar 

  20. Lowry OH, Rosenbrough NJ, Farr AL, Mondall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  21. McAdams MW, Roses AD (1980) Comparison of antigenic sources for acetylcholine receptor antibody assays in myasthenia gravis. Ann Neurol 8:61–66

    Google Scholar 

  22. Mittag T, Massa T, Kornfeld P, Papatestas A, Bender A, Genkins G (1981) Multiple forms of antiacetylcholine receptor antibody in Myasthenia gravis. Muscle Nerve 4:16–25

    Google Scholar 

  23. Mochly-Rosen D, Fuchs S (1981) Monoclonal anti-acetyl-choline-receptor antibodies directed against the cholinergic binding site. Biochemistry 20:5920–5924

    Google Scholar 

  24. Oosterhuis HJGH (1964) Studies in myasthenia gravis Part 1. A clinical study of 180 patients. J Neurol Sci 1:512–546

    Google Scholar 

  25. Oda K, Ito Y (1981) Myasthenia gravis: antibodies to acetylcholine receptor in ocular myasthenia gravis. J Neurol 225:251–258

    Google Scholar 

  26. Retz KC, Steele WJ (1977) Acid precipitation of protein in the presence of Triton X-100 and deoxycholate. Analyt Biochem 79:457–461

    Google Scholar 

  27. Richman DP, Gomez ChM, Berman PW, Burres SA, Fitch FW, Arnason BGW (1981) Monoclonal anti-acetylcholine receptor antibodies can cause experimental myasthenia. Nature 286:738–739

    Google Scholar 

  28. Roses AD, Olanow CW, McAdams MW, Lane RJM (1981) No direct correlation between serum antiacetylcholine receptor antibody levels and clinical state of individual patients with myasthenia gravis. Neurology 31:220–224

    Google Scholar 

  29. Schmidt J, Raftery MA (1973) A simple assay for the study of solubilized acetylcholine receptors. Analyt Biochem 52:349–354

    Google Scholar 

  30. Simpson JA (1960) Myasthenia gravis, a new hypothesis. Scot Med J 5:419–436

    Google Scholar 

  31. Tindall RSA, Kent M, Wells L (1981) A rapid immunoadsorbent radioimmunoassay for anti-acetylcholine receptor antibody. J Immunol Meth 45:1–14

    Google Scholar 

  32. Tindall RSA (1981) Humoral immunity in myasthenia gravis: biochemical characterisation of acquired antireceptor antibodies and clinical correlations. Ann Neurol 10:437–447

    Google Scholar 

  33. Toyka KV, Drachman DB, Pestron KA, Kao I (1975) Myasthenia gravis: passiv transfer from man to mouse. Science 90:397–399

    Google Scholar 

  34. Toyka KV, Becker T, Fateh-Moghadam A, Besinger UA, Brehm G, Neumeier D, Heiniger K, Birnberger KL (1979) Die Bedeutung der Bestimmung von Antikörpern gegen Acetylcholinreceptoren in der Diagnostik der Myasthenia gravis. Klin Wochenschr 57:937–942

    Google Scholar 

  35. Tzartos SJ, Seybold ME, Lindstrom JM (1982) Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies. Proc Natl Acad Sci USA 79:188–192

    Google Scholar 

  36. Vincent A, Newson-Davis J (1982) Acetylcholine receptor antibodies in myasthenia gravis. I. Patients with generalized myasthenia or disease restricted to ocular muscles. Clin Exp Immunol 49:257–265

    Google Scholar 

  37. Salzner HJ, Schmiedel N, Druschky KF, Kalies I, Kalden JR (1981) Concanavalin A-induced suppressor cells in the peripheral blood of myasthenia gravis patients. N Y Acad Sci 377:838–839

    Google Scholar 

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Authors and Affiliations

  1. Institut für klinische Immunologie und Rheumatologie, Universität Erlangen-Nürnberg, Germany

    I. Kalies & J. R. Kalden

  2. Zentrum Biochemie, Medizinische Hochschule Hannover, Germany

    F. Heinz

  3. Neurologische Universitätsklinik mit Poliklinik, Universität Erlangen-Nürnberg, Germany

    W. P. Kaschka & K. -F. Druschky

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  1. I. Kalies
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  2. F. Heinz
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  3. W. P. Kaschka
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  4. K. -F. Druschky
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  5. J. R. Kalden
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Gefördert durch Mittel der Deutschen Forschungsgemeinschaft (Ka 325/8)

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Kalies, I., Heinz, F., Kaschka, W.P. et al. Heterogenität von Acetylcholinrezeptor-Antikörpern bei Myasthenia gravis Patienten. Klin Wochenschr 62, 377–385 (1984). https://doi.org/10.1007/BF01716258

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  • DOI: https://doi.org/10.1007/BF01716258

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