Skip to main content
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1992 Jun;156(6):639–646.

Autoimmune disease and the nervous system. Biochemical, molecular, and clinical update.

J E Merrill 1, M C Graves 1, D G Mulder 1
PMCID: PMC1003353  PMID: 1319627

Abstract

Autoimmunity in the central and peripheral nervous system can manifest as the result of cellular or humoral immune responses to autoantigens. There is evidence that multiple sclerosis is a cell-mediated autoimmune disease of the central nervous system in which both myelin and the cell that produces the myelin are destroyed. Diseases such as acute inflammatory demyelinating polyneuropathy (also called Guillain-Barré syndrome) and myasthenia gravis are considered antibody-mediated diseases of the peripheral nervous system and neuromuscular junctions, respectively. We review these diseases and explore mechanisms of immune-mediated destruction of these nervous system components. We specifically focus on one effective therapy aimed at countering the immune attack, that of thymectomy in patients with myasthenia gravis.

Full text

PDF
639

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adorini L., Barnaba V., Bona C., Celada F., Lanzavecchia A., Sercarz E., Suciu-Foca N., Wekerle H. New perspectives on immunointervention in autoimmune diseases. Immunol Today. 1990 Nov;11(11):383–386. doi: 10.1016/0167-5699(90)90148-3. [DOI] [PubMed] [Google Scholar]
  2. Allegretta M., Nicklas J. A., Sriram S., Albertini R. J. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990 Feb 9;247(4943):718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
  3. Ando D. G., Clayton J., Kono D., Urban J. L., Sercarz E. E. Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. Cell Immunol. 1989 Nov;124(1):132–143. doi: 10.1016/0008-8749(89)90117-2. [DOI] [PubMed] [Google Scholar]
  4. Barna B. P., Chou S. M., Jacobs B., Yen-Lieberman B., Ransohoff R. M. Interferon-beta impairs induction of HLA-DR antigen expression in cultured adult human astrocytes. J Neuroimmunol. 1989 Jun;23(1):45–53. doi: 10.1016/0165-5728(89)90072-6. [DOI] [PubMed] [Google Scholar]
  5. Barohn R. J., Kissel J. T., Warmolts J. R., Mendell J. R. Chronic inflammatory demyelinating polyradiculoneuropathy. Clinical characteristics, course, and recommendations for diagnostic criteria. Arch Neurol. 1989 Aug;46(8):878–884. doi: 10.1001/archneur.1989.00520440064022. [DOI] [PubMed] [Google Scholar]
  6. Bartholomaeus W. N., O'Donoghue H., Foti D., Lawson C. M., Shellam G. R., Reed W. D. Multiple autoantibodies following cytomegalovirus infection: virus distribution and specificity of autoantibodies. Immunology. 1988 Jul;64(3):397–405. [PMC free article] [PubMed] [Google Scholar]
  7. Beck J., Rondot P., Catinot L., Falcoff E., Kirchner H., Wietzerbin J. Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations? Acta Neurol Scand. 1988 Oct;78(4):318–323. doi: 10.1111/j.1600-0404.1988.tb03663.x. [DOI] [PubMed] [Google Scholar]
  8. Bender B. S., Bennett R., Laughon B. E., Greenough W. B., 3rd, Gaydos C., Sears S. D., Forman M. S., Bartlett J. G. Is Clostridium difficile endemic in chronic-care facilities? Lancet. 1986 Jul 5;2(8497):11–13. doi: 10.1016/s0140-6736(86)92559-6. [DOI] [PubMed] [Google Scholar]
  9. Benveniste E. N., Sparacio S. M., Bethea J. R. Tumor necrosis factor-alpha enhances interferon-gamma-mediated class II antigen expression on astrocytes. J Neuroimmunol. 1989 Dec;25(2-3):209–219. doi: 10.1016/0165-5728(89)90139-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brajczewska-Fischer W., Iwińska B., Kruszewska J., Korlak J., Członkowska A. Interleukin 1 and 2 production by peripheral blood mononuclear cells in subacute sclerosing panencephalitis and exacerbation of multiple sclerosis. Acta Neurol Scand. 1989 Nov;80(5):390–393. doi: 10.1111/j.1600-0404.1989.tb03899.x. [DOI] [PubMed] [Google Scholar]
  11. Brashear H. R., Phillips L. H., 2nd Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology. 1991 Oct;41(10):1588–1592. doi: 10.1212/wnl.41.10.1588. [DOI] [PubMed] [Google Scholar]
  12. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  13. Calder V., Owen S., Watson C., Feldmann M., Davison A. MS: a localized immune disease of the central nervous system. Immunol Today. 1989 Mar;10(3):99–103. doi: 10.1016/0167-5699(89)90235-1. [DOI] [PubMed] [Google Scholar]
  14. Chung I. Y., Benveniste E. N. Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J Immunol. 1990 Apr 15;144(8):2999–3007. [PubMed] [Google Scholar]
  15. Clayton J. P., Gammon G. M., Ando D. G., Kono D. H., Hood L., Sercarz E. E. Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein. J Exp Med. 1989 May 1;169(5):1681–1691. doi: 10.1084/jem.169.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  17. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Diniz M. A., Cunha L., Gonçalves F., Oliveira C. Deux cas de syndrome de l'homme raide avec tremblement. Rev Neurol (Paris) 1986;142(12):918–920. [PubMed] [Google Scholar]
  19. Dore-Duffy P., Donaldson J. O., Koff T., Longo M., Perry W. Prostaglandin release in multiple sclerosis: correlation with disease activity. Neurology. 1986 Dec;36(12):1587–1590. doi: 10.1212/wnl.36.12.1587. [DOI] [PubMed] [Google Scholar]
  20. Drachman D. B., Kuncl R. W. Amyotrophic lateral sclerosis: an unconventional autoimmune disease? Ann Neurol. 1989 Aug;26(2):269–274. doi: 10.1002/ana.410260214. [DOI] [PubMed] [Google Scholar]
  21. Drachman D. B., de Silva S., Ramsay D., Pestronk A. Humoral pathogenesis of myasthenia gravis. Ann N Y Acad Sci. 1987;505:90–105. doi: 10.1111/j.1749-6632.1987.tb51285.x. [DOI] [PubMed] [Google Scholar]
  22. Dwyer D. S., Vakil M., Bradley R. J., Oh S. J., Kearney J. F. A possible cause of myasthenia gravis: idiotypic networks involving bacterial antigens. Ann N Y Acad Sci. 1987;505:461–471. doi: 10.1111/j.1749-6632.1987.tb51316.x. [DOI] [PubMed] [Google Scholar]
  23. Ellison G. W., Myers L. W. Immunosuppressive drugs in multiple sclerosis: pro and con. Neurology. 1980 Jul;30(7 Pt 2):28–32. doi: 10.1212/wnl.30.7_part_2.28. [DOI] [PubMed] [Google Scholar]
  24. Estes M. L., Rudick R. A., Barnett G. H., Ransohoff R. M. Stereotactic biopsy of an active multiple sclerosis lesion. Immunocytochemical analysis and neuropathologic correlation with magnetic resonance imaging. Arch Neurol. 1990 Dec;47(12):1299–1303. doi: 10.1001/archneur.1990.00530120043008. [DOI] [PubMed] [Google Scholar]
  25. Feldberg W., Gupta K. P. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol. 1973 Jan;228(1):41–53. doi: 10.1113/jphysiol.1973.sp010071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Fierz W., Endler B., Reske K., Wekerle H., Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J Immunol. 1985 Jun;134(6):3785–3793. [PubMed] [Google Scholar]
  27. Fontana A., Kristensen F., Dubs R., Gemsa D., Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed] [Google Scholar]
  28. Franciotta D. M., Grimaldi L. M., Martino G. V., Piccolo G., Bergamaschi R., Citterio A., Melzi d'Eril G. V. Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis. Ann Neurol. 1989 Dec;26(6):787–789. doi: 10.1002/ana.410260618. [DOI] [PubMed] [Google Scholar]
  29. Freeman B. A., Crapo J. D. Biology of disease: free radicals and tissue injury. Lab Invest. 1982 Nov;47(5):412–426. [PubMed] [Google Scholar]
  30. Gallo P., Piccinno M. G., Krzalic L., Tavolato B. Tumor necrosis factor alpha (TNF alpha) and neurological diseases. Failure in detecting TNF alpha in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumours. J Neuroimmunol. 1989 Jun;23(1):41–44. doi: 10.1016/0165-5728(89)90071-4. [DOI] [PubMed] [Google Scholar]
  31. Gallo P., Piccinno M. G., Pagni S., Argentiero V., Giometto B., Bozza F., Tavolato B. Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid. J Neurol Sci. 1989 Aug;92(1):9–15. doi: 10.1016/0022-510x(89)90171-8. [DOI] [PubMed] [Google Scholar]
  32. Gallo P., Piccinno M., Pagni S., Tavolato B. Interleukin-2 levels in serum and cerebrospinal fluid of multiple sclerosis patients. Ann Neurol. 1988 Dec;24(6):795–797. doi: 10.1002/ana.410240618. [DOI] [PubMed] [Google Scholar]
  33. Gebarski S. S., Gabrielsen T. O., Gilman S., Knake J. E., Latack J. T., Aisen A. M. The initial diagnosis of multiple sclerosis: clinical impact of magnetic resonance imaging. Ann Neurol. 1985 May;17(5):469–474. doi: 10.1002/ana.410170509. [DOI] [PubMed] [Google Scholar]
  34. Genkins G., Kornfeld P., Papatestas A. E., Bender A. N., Matta R. J. Clinical experience in more than 2000 patients with myasthenia gravis. Ann N Y Acad Sci. 1987;505:500–513. doi: 10.1111/j.1749-6632.1987.tb51318.x. [DOI] [PubMed] [Google Scholar]
  35. Giulian D., Lachman L. B. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science. 1985 Apr 26;228(4698):497–499. doi: 10.1126/science.3872478. [DOI] [PubMed] [Google Scholar]
  36. Gorin F., Baldwin B., Tait R., Pathak R., Seyal M., Mugnaini E. Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. Ann Neurol. 1990 Nov;28(5):711–714. doi: 10.1002/ana.410280518. [DOI] [PubMed] [Google Scholar]
  37. Greenstein J. I., McFarland H. F., Richert J. R. Characterization of antigen-specific T cells in multiple sclerosis twins with elevated proliferative responses to measles virus. J Immunol. 1986 Jul 15;137(2):546–550. [PubMed] [Google Scholar]
  38. Hafler D. A., Benjamin D. S., Burks J., Weiner H. L. Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. J Immunol. 1987 Jul 1;139(1):68–72. [PubMed] [Google Scholar]
  39. Hafler D. A., Duby A. D., Lee S. J., Benjamin D., Seidman J. G., Weiner H. L. Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. J Exp Med. 1988 Apr 1;167(4):1313–1322. doi: 10.1084/jem.167.4.1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Hafler D. A., Weiner H. L. Immunosuppression with monoclonal antibodies in multiple sclerosis. Neurology. 1988 Jul;38(7 Suppl 2):42–47. [PubMed] [Google Scholar]
  41. Hafler D. A., Weiner H. L. MS: a CNS and systemic autoimmune disease. Immunol Today. 1989 Mar;10(3):104–107. doi: 10.1016/0167-5699(89)90236-3. [DOI] [PubMed] [Google Scholar]
  42. Hammann K. P., Nix W., Dierich M. P., Hopf H. C. Multiple sclerosis patients show an increased spontaneous activity of their peripheral blood monocytes as measured by chemiluminescence. Acta Neurol Scand. 1983 Sep;68(3):151–156. doi: 10.1111/j.1600-0404.1983.tb05341.x. [DOI] [PubMed] [Google Scholar]
  43. Hauser S. L., Doolittle T. H., Lincoln R., Brown R. H., Dinarello C. A. Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology. 1990 Nov;40(11):1735–1739. doi: 10.1212/wnl.40.11.1735. [DOI] [PubMed] [Google Scholar]
  44. Hirsch R. L., Panitch H. S., Johnson K. P. Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferon in vitro. J Clin Immunol. 1985 Nov;5(6):386–389. doi: 10.1007/BF00915335. [DOI] [PubMed] [Google Scholar]
  45. Hofman F. M., Hinton D. R., Johnson K., Merrill J. E. Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med. 1989 Aug 1;170(2):607–612. doi: 10.1084/jem.170.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Hofman F. M., von Hanwehr R. I., Dinarello C. A., Mizel S. B., Hinton D., Merrill J. E. Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. J Immunol. 1986 May 1;136(9):3239–3245. [PubMed] [Google Scholar]
  47. Hunter M. I., Nlemadim B. C., Davidson D. L. Lipid peroxidation products and antioxidant proteins in plasma and cerebrospinal fluid from multiple sclerosis patients. Neurochem Res. 1985 Dec;10(12):1645–1652. doi: 10.1007/BF00988606. [DOI] [PubMed] [Google Scholar]
  48. Jaretzki A., 3rd, Penn A. S., Younger D. S., Wolff M., Olarte M. R., Lovelace R. E., Rowland L. P. "Maximal" thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg. 1988 May;95(5):747–757. [PubMed] [Google Scholar]
  49. Keesey J., Naiem F., Lindstrom J., Roe D., Herrmann C., Jr, Walford R. Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis. Arch Neurol. 1982 Feb;39(2):73–77. doi: 10.1001/archneur.1982.00510140007002. [DOI] [PubMed] [Google Scholar]
  50. Kittur S. D., Kittur D. S., Soncrant T. T., Rapoport S. I., Tourtellotte W. W., Nagel J. E., Adler W. H. Soluble interleukin-2 receptors in cerebrospinal fluid from individuals with various neurological disorders. Ann Neurol. 1990 Aug;28(2):168–173. doi: 10.1002/ana.410280209. [DOI] [PubMed] [Google Scholar]
  51. Knobler R. L., Panitch H. S., Braheny S. L., Sipe J. C., Rice G. P., Huddlestone J. R., Francis G. S., Hooper C. K., Kamin-Lewis R. M., Johnson K. P. Systemic alpha-interferon therapy of multiple sclerosis. Neurology. 1984 Oct;34(10):1273–1279. doi: 10.1212/wnl.34.10.1273. [DOI] [PubMed] [Google Scholar]
  52. Kono D. H., Urban J. L., Horvath S. J., Ando D. G., Saavedra R. A., Hood L. Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice. J Exp Med. 1988 Jul 1;168(1):213–227. doi: 10.1084/jem.168.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Krah D. L., Choppin P. W. Mice immunized with measles virus develop antibodies to a cell surface receptor for binding virus. J Virol. 1988 May;62(5):1565–1572. doi: 10.1128/jvi.62.5.1565-1572.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Lachman L. B., Brown D. C., Dinarello C. A. Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line. J Immunol. 1987 May 1;138(9):2913–2916. [PubMed] [Google Scholar]
  55. Leist T. P., Frei K., Kam-Hansen S., Zinkernagel R. M., Fontana A. Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients. J Exp Med. 1988 May 1;167(5):1743–1748. doi: 10.1084/jem.167.5.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Lieberman A. P., Pitha P. M., Shin H. S., Shin M. L. Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6348–6352. doi: 10.1073/pnas.86.16.6348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Lorish T. R., Thorsteinsson G., Howard F. M., Jr Stiff-man syndrome updated. Mayo Clin Proc. 1989 Jun;64(6):629–636. doi: 10.1016/s0025-6196(12)65339-7. [DOI] [PubMed] [Google Scholar]
  58. Massa P. T., Schimpl A., Wecker E., ter Meulen V. Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7242–7245. doi: 10.1073/pnas.84.20.7242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. McFarlin D. E., McFarland H. F. Multiple sclerosis (first of two parts). N Engl J Med. 1982 Nov 4;307(19):1183–1188. doi: 10.1056/NEJM198211043071905. [DOI] [PubMed] [Google Scholar]
  60. Merrill J. E. Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Dev Neurosci. 1991;13(3):130–137. doi: 10.1159/000112150. [DOI] [PubMed] [Google Scholar]
  61. Merrill J. E., Gerner R. H., Myers L. W., Ellison G. W. Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 1. Association between amount of prostaglandin produced, natural killer, and endogenous interferon. J Neuroimmunol. 1983 Jun;4(3):223–237. doi: 10.1016/0165-5728(83)90037-1. [DOI] [PubMed] [Google Scholar]
  62. Merrill J. E., Kagan J. M., Schmid I., Strom S. R., Quan S. G., Chen I. S. T cell lines established from multiple sclerosis cerebrospinal fluid T cells using human retroviruses. J Neuroimmunol. 1989 Feb;21(2-3):213–226. doi: 10.1016/0165-5728(89)90177-x. [DOI] [PubMed] [Google Scholar]
  63. Merrill J. E., Mohlstrom C., Uittenbogaart C., Kermaniarab V., Ellison G. W., Myers L. W. Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis. J Immunol. 1984 Oct;133(4):1931–1937. [PubMed] [Google Scholar]
  64. Merrill J. E., Strom S. R., Ellison G. W., Myers L. W. In vitro study of mediators of inflammation in multiple sclerosis. J Clin Immunol. 1989 Mar;9(2):84–96. doi: 10.1007/BF00916935. [DOI] [PubMed] [Google Scholar]
  65. Merrill J. E., Zimmerman R. P. Natural and induced cytotoxicity of oligodendrocytes by microglia is inhibitable by TGF beta. Glia. 1991;4(3):327–331. doi: 10.1002/glia.440040311. [DOI] [PubMed] [Google Scholar]
  66. Mickey M. R., Ellison G. W., Fahey J. L., Moody D. J., Myers L. W. Correlation of clinical and immunologic states in multiple sclerosis. Arch Neurol. 1987 Apr;44(4):371–375. doi: 10.1001/archneur.1987.00520160013006. [DOI] [PubMed] [Google Scholar]
  67. Milanese C., Salmaggi A., la Mantia L., Corridori F., Nespolo A. Intrathecal beta-interferon in multiple sclerosis. Lancet. 1988 Sep 3;2(8610):563–564. doi: 10.1016/s0140-6736(88)92676-1. [DOI] [PubMed] [Google Scholar]
  68. Mulder D. G., Graves M., Herrmann C. Thymectomy for myasthenia gravis: recent observations and comparisons with past experience. Ann Thorac Surg. 1989 Oct;48(4):551–555. doi: 10.1016/s0003-4975(10)66861-0. [DOI] [PubMed] [Google Scholar]
  69. Mulder D. G., Herrmann C., Jr, Keesey J., Edwards H. Thymectomy for myasthenia gravis. Am J Surg. 1983 Jul;146(1):61–66. doi: 10.1016/0002-9610(83)90260-x. [DOI] [PubMed] [Google Scholar]
  70. Myers L. W., Fahey J. L., Moody D. J., Mickey M. R., Frane M. V., Ellison G. W. Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial. Arch Neurol. 1987 Aug;44(8):828–832. doi: 10.1001/archneur.1987.00520200032014. [DOI] [PubMed] [Google Scholar]
  71. Nadal D., Leppert D., Frei K., Gallo P., Lamche H., Fontana A. Tumour necrosis factor-alpha in infectious meningitis. Arch Dis Child. 1989 Sep;64(9):1274–1279. doi: 10.1136/adc.64.9.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. 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]
  73. Nobile-Orazio E., Baldini L., Barbieri S., Marmiroli P., Spagnol G., Francomano E., Scarlato G. Treatment of patients with neuropathy and anti-MAG IgM M-proteins. Ann Neurol. 1988 Jul;24(1):93–97. doi: 10.1002/ana.410240118. [DOI] [PubMed] [Google Scholar]
  74. Oger J., Kastrukoff L., O'Gorman M., Paty D. W. Progressive multiple sclerosis: abnormal immune functions in vitro and aberrant correlation with enumeration of lymphocyte subpopulations. J Neuroimmunol. 1986 Jul;12(1):37–48. doi: 10.1016/0165-5728(86)90095-0. [DOI] [PubMed] [Google Scholar]
  75. Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
  76. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  77. Olsson T., Zhi W. W., Höjeberg B., Kostulas V., Jiang Y. P., Anderson G., Ekre H. P., Link H. Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma. J Clin Invest. 1990 Sep;86(3):981–985. doi: 10.1172/JCI114800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Panitch H. S., Hirsch R. L., Haley A. S., Johnson K. P. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet. 1987 Apr 18;1(8538):893–895. doi: 10.1016/s0140-6736(87)92863-7. [DOI] [PubMed] [Google Scholar]
  79. Panitch H. S., Hirsch R. L., Schindler J., Johnson K. P. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology. 1987 Jul;37(7):1097–1102. doi: 10.1212/wnl.37.7.1097. [DOI] [PubMed] [Google Scholar]
  80. Papatestas A. E., Genkins G., Kornfeld P., Eisenkraft J. B., Fagerstrom R. P., Pozner J., Aufses A. H., Jr Effects of thymectomy in myasthenia gravis. Ann Surg. 1987 Jul;206(1):79–88. doi: 10.1097/00000658-198707000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Paty D. W., McFarlin D. E., McDonald W. I. Magnetic resonance imaging and laboratory aids in the diagnosis of multiple sclerosis. Ann Neurol. 1991 Jan;29(1):3–5. doi: 10.1002/ana.410290103. [DOI] [PubMed] [Google Scholar]
  82. Pestronk A., Adams R. N., Kuncl R. W., Drachman D. B., Clawson L. L., Cornblath D. R. Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders. Neurology. 1989 May;39(5):628–633. doi: 10.1212/wnl.39.5.628. [DOI] [PubMed] [Google Scholar]
  83. Pestronk A., Chaudhry V., Feldman E. L., Griffin J. W., Cornblath D. R., Denys E. H., Glasberg M., Kuncl R. W., Olney R. K., Yee W. C. Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies. Ann Neurol. 1990 Mar;27(3):316–326. doi: 10.1002/ana.410270314. [DOI] [PubMed] [Google Scholar]
  84. Pestronk A., Cornblath D. R., Ilyas A. A., Baba H., Quarles R. H., Griffin J. W., Alderson K., Adams R. N. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol. 1988 Jul;24(1):73–78. doi: 10.1002/ana.410240113. [DOI] [PubMed] [Google Scholar]
  85. Philip R., Epstein L. B. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature. 1986 Sep 4;323(6083):86–89. doi: 10.1038/323086a0. [DOI] [PubMed] [Google Scholar]
  86. Prineas J. W., Graham J. S. Multiple sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann Neurol. 1981 Aug;10(2):149–158. doi: 10.1002/ana.410100205. [DOI] [PubMed] [Google Scholar]
  87. Racke M. K., Dhib-Jalbut S., Cannella B., Albert P. S., Raine C. S., McFarlin D. E. Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. J Immunol. 1991 May 1;146(9):3012–3017. [PubMed] [Google Scholar]
  88. Ravindranath R. M., Graves M. C. Attenuated murine cytomegalovirus binds to N-acetylglucosamine, and shift to virulence may involve recognition of sialic acids. J Virol. 1990 Nov;64(11):5430–5440. doi: 10.1128/jvi.64.11.5430-5440.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Robbins D. S., Shirazi Y., Drysdale B. E., Lieberman A., Shin H. S., Shin M. L. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol. 1987 Oct 15;139(8):2593–2597. [PubMed] [Google Scholar]
  90. Roobol T. H., Kazzaz B. A., Vecht C. J. Segmental rigidity and spinal myoclonus as a paraneoplastic syndrome. J Neurol Neurosurg Psychiatry. 1987 May;50(5):628–631. doi: 10.1136/jnnp.50.5.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Rotteveel F. T., Kuenen B., Kokkelink I., Meager A., Lucas C. J. Relative increase of inflammatory CD4+ T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals. Clin Exp Immunol. 1990 Jan;79(1):15–20. doi: 10.1111/j.1365-2249.1990.tb05120.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Rowland L. P. Therapy in myasthenia gravis: introduction. Ann N Y Acad Sci. 1987;505:566–567. doi: 10.1111/j.1749-6632.1987.tb51324.x. [DOI] [PubMed] [Google Scholar]
  93. Sanders D. B. The electrodiagnosis of myasthenia gravis. Ann N Y Acad Sci. 1987;505:539–556. doi: 10.1111/j.1749-6632.1987.tb51322.x. [DOI] [PubMed] [Google Scholar]
  94. Sawada M., Kondo N., Suzumura A., Marunouchi T. Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 1989 Jul 10;491(2):394–397. doi: 10.1016/0006-8993(89)90078-4. [DOI] [PubMed] [Google Scholar]
  95. Sayetta R. B. Theories of the etiology of multiple sclerosis: a critical review. J Clin Lab Immunol. 1986 Oct;21(2):55–70. [PubMed] [Google Scholar]
  96. Seboun E., Robinson M. A., Doolittle T. H., Ciulla T. A., Kindt T. J., Hauser S. L. A susceptibility locus for multiple sclerosis is linked to the T cell receptor beta chain complex. Cell. 1989 Jun 30;57(7):1095–1100. doi: 10.1016/0092-8674(89)90046-9. [DOI] [PubMed] [Google Scholar]
  97. Selmaj K. W., Farooq M., Norton W. T., Raine C. S., Brosnan C. F. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol. 1990 Jan 1;144(1):129–135. [PubMed] [Google Scholar]
  98. Selmaj K. W., Raine C. S. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988 Apr;23(4):339–346. doi: 10.1002/ana.410230405. [DOI] [PubMed] [Google Scholar]
  99. Selmaj K., Nowak Z., Tchórzewski H. Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells in multiple sclerosis patients. J Neurol Sci. 1988 May;85(1):67–76. doi: 10.1016/0022-510x(88)90036-6. [DOI] [PubMed] [Google Scholar]
  100. Selmaj K., Nowak Z., Tchórzewski H. Multiple sclerosis: effect of myelin basic protein on interleukin 1, interleukin 2 production and interleukin 2 receptor expression in vitro. Clin Exp Immunol. 1988 Jun;72(3):428–433. [PMC free article] [PubMed] [Google Scholar]
  101. Solimena M., Folli F., Aparisi R., Pozza G., De Camilli P. Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl J Med. 1990 May 31;322(22):1555–1560. doi: 10.1056/NEJM199005313222202. [DOI] [PubMed] [Google Scholar]
  102. Solimena M., Folli F., Denis-Donini S., Comi G. C., Pozza G., De Camilli P., Vicari A. M. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med. 1988 Apr 21;318(16):1012–1020. doi: 10.1056/NEJM198804213181602. [DOI] [PubMed] [Google Scholar]
  103. Traugott U., Lebon P. Interferon-gamma and Ia antigen are present on astrocytes in active chronic multiple sclerosis lesions. J Neurol Sci. 1988 Apr;84(2-3):257–264. doi: 10.1016/0022-510x(88)90130-x. [DOI] [PubMed] [Google Scholar]
  104. Traugott U. Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol. 1987 Oct;16(2):283–302. doi: 10.1016/0165-5728(87)90082-8. [DOI] [PubMed] [Google Scholar]
  105. Trojaborg W., Galassi G., Hays A. P., Lovelace R. E., Alkaitis M., Latov N. Electrophysiologic study of experimental demyelination induced by serum of patients with IgM M proteins and neuropathy. Neurology. 1989 Dec;39(12):1581–1586. doi: 10.1212/wnl.39.12.1581. [DOI] [PubMed] [Google Scholar]
  106. Trotter J. L., Clifford D. B., McInnis J. E., Griffeth R. C., Bruns K. A., Perlmutter M. S., Anderson C. B., Collins K. G., Banks G., Hicks B. C. Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis. Ann Neurol. 1989 Feb;25(2):172–178. doi: 10.1002/ana.410250211. [DOI] [PubMed] [Google Scholar]
  107. Trotter J. L., van der Veen R. C., Clifford D. B. Serial studies of serum interleukin-2 in chronic progressive multiple sclerosis patients: occurrence of 'bursts' and effect of cyclosporine. J Neuroimmunol. 1990 Jun;28(1):9–14. doi: 10.1016/0165-5728(90)90036-m. [DOI] [PubMed] [Google Scholar]
  108. Tsunawaki S., Sporn M., Ding A., Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature. 1988 Jul 21;334(6179):260–262. doi: 10.1038/334260a0. [DOI] [PubMed] [Google Scholar]
  109. Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
  110. Vincent A., Lang B., Newsom-Davis J. Autoimmunity to the voltage-gated calcium channel underlies the Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder. Trends Neurosci. 1989 Dec;12(12):496–502. doi: 10.1016/0166-2236(89)90109-4. [DOI] [PubMed] [Google Scholar]
  111. Williams D. B., Windebank A. J. Motor neuron disease (amyotrophic lateral sclerosis). Mayo Clin Proc. 1991 Jan;66(1):54–82. doi: 10.1016/s0025-6196(12)61175-6. [DOI] [PubMed] [Google Scholar]
  112. Wong G. H., Clark-Lewis I., Harris A. W., Schrader J. W. Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin. Eur J Immunol. 1984 Jan;14(1):52–56. doi: 10.1002/eji.1830140110. [DOI] [PubMed] [Google Scholar]
  113. Woodroofe M. N., Bellamy A. S., Feldmann M., Davison A. N., Cuzner M. L. Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis. Possible role for microglia in lesion growth. J Neurol Sci. 1986 Jul;74(2-3):135–152. doi: 10.1016/0022-510x(86)90100-0. [DOI] [PubMed] [Google Scholar]
  114. Zamvil S. S., Mitchell D. J., Moore A. C., Kitamura K., Steinman L., Rothbard J. B. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature. 1986 Nov 20;324(6094):258–260. doi: 10.1038/324258a0. [DOI] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES