Skip to main content
SpringerLink
Log in

Myasthenia gravis: Overlap with ‘polyendocrine’ autoimmunity

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

81 patients with spontaneously acquired myasthenia gravis (MG) were investigated for the presence of autoimmune (AI) diseases and their sera were tested for a range of organ-specific autoantibodies. 77 of the patients were HLA-phenotyped. Antibody titres to acetylcholine receptors (AChR) were higher in non-thymomatous patients who possessed HLA-B8 (p<0.05) and/or -DR3 (p<0.05) as compared to patients lacking these HLA antigens. 3 out of 20 (15%) patients with ocular MG, 7/23 (30%) with generalized MG of early onset, 11/23 (48%) generalized MG of late onset and 5/14 (35%) patients with thymoma had either overt AI diseases or significant titres of organ-specific autoantibodies suggesting subclinical AI disease. In ocular MG, low titres and an infrequent finding of antibodies to AChR (32%) as well as the low prevalence of associated autoantibodies and AI diseases indicate that this subgroup of MG consists of patients with restricted AI reactivity. HLA-B8and -DR3 were present in all the patients with associated AI disorders in the young onset group but in none of the patients with old age of onset. In the young group, 6 out of 7 patients with associated AI conditions were women whereas the sex ratio was about equal in the older cases in both, patients with and without associated AI diseases or autoantibodies. We conclude from these observations that ageing provides conditions that allow the breakdown of self tolerance. The simultaneous presence of HLA B8, DR3 and female sex provide important additional factors for early expression of MG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Basedow von (1984) Exophthalmos durch Hypertrophie des Zellgewebes in der Augenhöhle. Wochenschr ges Heilkd 13:197–228

    Google Scholar 

  2. Becker KL, Titus JL, McConahey WM, Woolner LB (1964) Morphologic evidence of thyroiditis in myasthenia gravis. JAMA 187:994–996

    Google Scholar 

  3. Bertoye A, Garin JP, Beaupere A, Morne R, Saubier, Monier P, Woehrle R (1968) Association de myasthenie et d'hyperthyroidie. A propos d'une observation. Lyon Med 28:67–79

    Google Scholar 

  4. Bodmer JG, Pickbourne P, Richards S (1978) Report of the Seventh Int. Histocompatibility Workshop and Conference Oxford. Bodmer WF, Batchelor JR, Bodmer JG, Festenstein H, Morris PJ (eds) In: Histocompatibility Testing 1977. pp 35–84

  5. Bottazzo GF, Dean BM, Gorsuch AN, Cudworth AG, Doniach D (1980) Complement-fixing islet-cell antibodies in Typ I diabetes: possible monitors of active beta cell damage. Lancet I:668–672

    Google Scholar 

  6. Boudin C, Lhuillier M, Schaison G, Patri B, Girault F (1972) Myasthenie, vitiligo, maladie de Basedow. Ann Med Interne 123:861–864

    Google Scholar 

  7. Boulet P, Passouant P, Mirouze J, Barjon P, Temple M (1959) Myasthenie avec maladic d'Addison. Thymome metastatique phrenopulmonaire. Ann Endocrinol 20:740–747

    Google Scholar 

  8. Bundey S, Doniach D, Soothill JF (1972) Immunological studies in patients with juvenile-onset myasthenia gravis and in their relatives. Clin Exp Immunol 11:321–332

    Google Scholar 

  9. Castleman B, Norris EH (1949) The pathology of the thymus gland in myasthenia gravis. A study of 35 cases. Medicine 28:27–58

    Google Scholar 

  10. Christy M, Deckert T, Nerup J (1977) Immunity and autoimmunity in diabetes mellitus. Clin Endocrinol Metab 6:305–332

    Google Scholar 

  11. Compston DAS, Vincent A, Newsom-Davis J, Batchelor JR (1980) Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 103:579–601

    Google Scholar 

  12. Delrieu F, Menkes CJ, Sainte-Croix A, Babinet P, Chesneau AM, Delbarre F (1976) Myasthénie et thyroïdite autoimmune au cours due traitement de la polyarthrite par la D-Pénicillamine. Etude anatomo-clinique d'un cas. Ann Med Interne 127:739–743

    Google Scholar 

  13. Doniach D, Bottazzo GF (1981) Polyendocrine autoimmunity. In: Franklin EC (ed) Clinical immunology update. Elsevier, New York, pp 22–33

    Google Scholar 

  14. Drachman DB (1962) Myasthenia gravis and the thyroid gland. N Engl J Med 15:330–333

    Google Scholar 

  15. Drachman DB (1978) Myasthenia gravis. N Engl J Med 298:136–193

    Google Scholar 

  16. Durston JHJ (1969) Myasthenia gravis, Hashimoto's disease and pernicious anaemia. Postgrad Med J 45:290–291

    Google Scholar 

  17. Engel AG (1961) Thyroid function and myasthenia gravis. Arch Neurol 4:663–674

    Google Scholar 

  18. Engel AG (1979) Myasthenia gravis. In: Winken PJ, Bruyn GW (eds) Handbook of clinical neurology, Vol 41, Part II. Amsterdam, North-Holland, pp 95–145

  19. Farid NR, Simpson L, Noel EP, Barnard JM, Mandeville R, Larsen B, Marshall WH, Carter ND (1979) A study of human leucocyte D locus related antigens in Graves' disease. J Clin Invest 63:108–113

    Google Scholar 

  20. Feltkamp TW, Van Den Berg-Loonen PM, Nijenhuis LE, Engelfriet CP, Van Rossum AL, Van Loghem JJ, Oosterhuis JGH (1974) Myasthenia gravis, autoantibodies and HLA antigens. Br Med J 1:131–133

    Google Scholar 

  21. Fischer KC, Schartzmann RJ (1976) Oral corticosteroids in the treatment of ocular myasthenia gravis. Ann NY Acad Sci 274:652–658

    Google Scholar 

  22. Fritze D, Herrman C, Naeim F, Smith GS, Walford RL (1974) HLA antigens in myasthenia gravis. Lancet I:240–242

    Google Scholar 

  23. Fujita K, Yamada N, Sanbe T, Yudo T, Tsuchiya M, Shimabukuro K, Itoh K, Saito M (1970) Haemagglutination test utilizing the microsomal antigen from thyroid epithelial cells. Clin Pathol (Japan) 18:213–218

    Google Scholar 

  24. Galbraith RF, Summerskill WHJ, Murray J (1964) Systemic lupus erythematosus, cirrhosis and ulcerative colitis after thymectomy for myasthenia gravis. N Engl J Med 270:229–232

    Google Scholar 

  25. Garlepp MJ, Dawkins RL, Christiansen FT, Lawton J, Luciani G, McLeod J, Bradley J, Genkins G, Teng CS (1981) Autoimmunity in ocular and generalized myasthenia gravis. J Neuroimmunol 1:325–332

    Google Scholar 

  26. Goulon M, Gajdos P, Estournet B, Andre C, Tulliez M (1980) Myasthénie et maladies associées. Étude d'une série dc 145 cas. Ann Med Interne 131:9–16

    Google Scholar 

  27. Habermann J, Heinze HG, Horn K, Kantlehner R, Marschner I, Neumann J, Scriba PC (1975) Alimentärer Jodmangel in der Bundesrepublik Deutschland. Dtsch Med Wochenschr 100:1937–1945

    Google Scholar 

  28. Howard FM, Silverstein NM, Mulder DW (1965) The coexistence of myasthenia gravis and pernicious anemia. Am J Med Sci 250:518–526

    Google Scholar 

  29. Kaakinen A, Pirskanen R, Tiilikainen A (1975) LD antigens associated with HL-A8 and myasthenia gravis. Tissue Antigens 6:175–182

    Google Scholar 

  30. Kao I, Drachman DB (1977) Thymic muscle cells bear acetylcholine receptors; possible relation to myasthenia gravis. Science 195:74–75

    Google Scholar 

  31. Kirkpatrick CH, Windhorst DB (1979) Mucocutaneous candidiasis and thymoma. An J Med 66:939–945

    Google Scholar 

  32. 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 

  33. Maize JC, Lynch PJ, Arbor A (1972) Chronic mucocutanoues candidiasis of the adult. Arch Derm 105:96–98

    Google Scholar 

  34. Montes LF, Ceballos R, Cooper MD, Bradley MN, Bockman DE (1972) Chronic mucocutaneous candidiasis, myositis and thymoma. JAMA 222:1619–1623

    Google Scholar 

  35. Müller C, Fink D, Müller G, Wernet P (1980) Avoidance of certain systematic pitfalls in the detection of HLA-DR antibodies defining fine specificities. Tissue Antigens 16:244–253

    Google Scholar 

  36. Naeim F, Keesey JC, Harrmann C, Lindstrom J, Zeller E, Walford RL (1978) Association of HLA-B8, DRw3, and antiacetylcholine receptor antibodies in myasthenia gravis. Tissue Antigens 12:381–386

    Google Scholar 

  37. Newsom-Davis J, Willcox N, Calder L (1981) Thymus cells in myasthenia gravis selectively enhance production of antiacetylcholine-receptor antibody by autologous blood lymphocytes. N Engl J Med 305:1313–1318

    Google Scholar 

  38. Newsom-Davis J, Vincent A, Willcox N (1982) Acctylcholine receptor antibody: clinical and experimental aspects. In: Receptors, antibodies and disease. Pitman, London (Ciba Foundation Symposium 90), pp 225–247

    Google Scholar 

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

    Google Scholar 

  40. Robbins JJ, Burkle JS (1960) Association of myasthenia gravis and hyperthyroidism, showing reciprocal relationship. Report of a case and review of the literature. Ann Intern Med 52:890–893

    Google Scholar 

  41. Sachs JA (1979) The relevance of HLA antigens in some neurological diseases. In: Rose, FC (ed) Clinical neuroimmunology. Blackwell Scientific Publications, Oxford, pp 42–52

    Google Scholar 

  42. Säfwenberg J, Hammarström L, Lindblom JB, Matcll G, Möller E, Ostermann PO, Smith CI (1978) HLA-A,-B, and -D antigens in male patients with myasthenia gravis. Tissue Antigens 12:136–142

    Google Scholar 

  43. Sahay BH, Blendis LH, Greene R (1965) Relation between myasthenia gravis and thyroid disease. Br Med J 1:762–765

    Google Scholar 

  44. Schoch EP (1971) Thymic conversion of candida albicans from commensalism to pathogenism. Arch Derm 103:311–319

    Google Scholar 

  45. Scherbaum WA, Berg PA (1981) Bedeutung von Autoantikörpern in der Diagnostik endokrinologischer Erkrankungen. Dtsch Med Wochenschr 106:308–313

    Google Scholar 

  46. Scherbaum WA, Berg PA (1982) Development of adrenocortical failure in non-addisonian patients with antibodies to adrenal cortex. A clinical follow-up study. Clin Endocrinol 16:345–352

    Google Scholar 

  47. Scherbaum WA, Stöckle G, Wichmann J, Berg PA (1982) Immunological and clinical characterization of patients with untreated euthyroid and hypothyroid autoimmune thyroiditis. Antibody spectrum, response to TRH and clinical study. Acta Endocrinol 100:373–381

    Google Scholar 

  48. Schumm F, Stöhr M (1978) Myasthene Syndrome unter Penicillamin-Therapie. Klin Wochenschr 56:139–144

    Google Scholar 

  49. Schumm F, Wiethölter H, Fateh-Moghadam A (1981) Myasthenie-Syndrom unter Chloroquin-Therapie. Dtsch Med Wochenschr 106:1745–1747

    Google Scholar 

  50. Segal BM, Weintraub MI (1976) Hashimoto's thyroiditis, myasthenia gravis, idiopathic thrombocytopenic purpura. Ann Intern Med 85:761–762

    Google Scholar 

  51. Simpson JA (1958) An evaluation of thymectomy in myasthenia gravis. Brain 81:112–114

    Google Scholar 

  52. Simpson JA (1960) Myasthenia gravis. A new hypothesis. Scott Med J 5:419–436

    Google Scholar 

  53. Simpson JA (1964) Immunological disturbances in myasthenia gravis with a report of Hashimoto's disease developing after thymectomy. J Neurol Neurosurg Psychiatr 27:485–492

    Google Scholar 

  54. Singer W, Sahay BN (1966) Myasthenia gravis, Hashimoto's thyroiditis and pernicious anemia. Br Med J 1:904

    Google Scholar 

  55. Strauss AJL, van der Geld HWR, Kemp PG Jr, Exum ED, Goodman HC (1965) Immunological concomitans of myasthenia gravis. Ann NY Acad Sci 124:744–766

    Google Scholar 

  56. Terasaki P (1972) In: Ray JG (ed) Manual of tissue typing techniques. Natl Inst Health Bethesda, Maryland, pp 50–55

    Google Scholar 

  57. Thomsen M, Platz P, Andersen OO, Christy M, Lyngsoe J, Nerup J, Rasmussen K, Ryder L, Nielsen S, Svejgaard A (1975) MLC typing in juvenile diabetes mellitus and idiopathic Addison's disease. Transplant Rev 22:125–147

    Google Scholar 

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

    Google Scholar 

  59. Veenhoven WA, Oosterhuis HJ, van der Schans GS (1979) Myasthenia gravis and Werlhof's disease. Acta Med Scand 206:131–135

    Google Scholar 

  60. Vincent A, Newsom-Davis J (1979)α-Bungarotoxin and anti-acetylcholine receptor antibody binding to human acctylcholine receptor. Adv Cytopharmacol 3:269–278

    Google Scholar 

  61. Vincent A, Newsom-Davis J (1980) Anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiat 43:590–600

    Google Scholar 

  62. Vincent A (1981) Immunology of myasthenia gravis: Recent developments. Clin Immunol Allergy 1:161–179

    Google Scholar 

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

    Google Scholar 

  64. Wekerle H, Hohlfeld R, Ketelsen U-P, Kalden JR, Kalies I (1981) Thymic myogenesis, T-lymphocytes and the pathogenesis of myasthenia gravis. Ann NY Acad Sci 377:455–476

    Google Scholar 

  65. Weickhardt GD, Redmond AJ (1960) Myasthenia gravis and hyperthyroidism: report of two cases and review of the literature. Ann Intern Med 52:1246–1257

    Google Scholar 

  66. Witebsky E, Rose NR (1956) Studies on organ specificity. IV. Production of rabbit thyroid antibodies in the rabbit. J Immunol 76:408–416

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Poliklinik, University of Tübingen, Germany

    W. A. Scherbaum & F. J. Seif

  2. Neurologische Klinik, University of Tübingen, Germany

    F. Schumm

  3. Medizinische Klinik, University of Tübingen, Germany

    B. Maisch, Claudia Müller & P. A. Berg

  4. Department of Urology, Chirurgische Klinik, University of Tübingen, Germany

    S. H. Flüchter

  5. Institute of Clinical Chemistry Grosshadern, University of Munich, Germany

    A. Fateh-Moghadam

  6. Department of Immunology, Middlesex Hospital Medical School, London

    G. F. Bottazzo

Authors
  1. W. A. Scherbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Schumm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Maisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Fateh-Moghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. H. Flüchter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. J. Seif
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. F. Bottazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. A. Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was finalized when W.A. Scherbaum was a research associate at the Department of Immunology, Middle-sex Hospital Medical School, London, U.K. W.A. Scherbaum is supported by the Deutsche Forschungsgemeinschaft Sche 225/1–2

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scherbaum, W.A., Schumm, F., Maisch, B. et al. Myasthenia gravis: Overlap with ‘polyendocrine’ autoimmunity. Klin Wochenschr 61, 509–515 (1983). https://doi.org/10.1007/BF01488718

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01488718

Key words

Search

Navigation