Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1994 Nov;57(Suppl):65–68. doi: 10.1136/jnnp.57.suppl.65

Promotion of remyelination by polyclonal immunoglobulin in Theiler's virus-induced demyelination and in multiple sclerosis.

B G van Engelen 1, D J Miller 1, K D Pavelko 1, O R Hommes 1, M Rodriguez 1
PMCID: PMC1016730  PMID: 7964859

Abstract

Spontaneous remyelination occurs in experimental models of demyelination and in patients with multiple sclerosis, although to a limited extent. This enables the search for factors that promote remyelination. Using the Theiler's virus model of central nervous system demyelination, promotion of remyelination was observed after passive transfer of CNS-specific antiserum and transfer of CNS-specific purified immunoglobulin. Mouse polyclonal immunoglobulin from normal non-syngeneic mice, comparable with the human immunoglobulin preparation, also promotes CNS remyelination in the Theiler's virus model of multiple sclerosis. These experimental findings further bridge the gap with a pilot study that suggests clinical improvement after polyclonal immunoglobulin administration, possibly due to remyelination, in some multiple sclerosis patients with stable, steroid-unresponsive optic neuritis. In view of these experimental and clinical data, the physiological role of myelin in demyelination and remyelination is discussed, and the role of IgG solely as a deleterious molecule in the pathophysiology of multiple sclerosis and experimental demyelination is addressed.

Full text

PDF
68

Selected References

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

  1. Achiron A., Pras E., Gilad R., Ziv I., Mandel M., Gordon C. R., Noy S., Sarova-Pinhas I., Melamed E. Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis. Arch Neurol. 1992 Dec;49(12):1233–1236. doi: 10.1001/archneur.1992.00530360031013. [DOI] [PubMed] [Google Scholar]
  2. Bansal R., Gard A. L., Pfeiffer S. E. Stimulation of oligodendrocyte differentiation in culture by growth in the presence of a monoclonal antibody to sulfated glycolipid. J Neurosci Res. 1988 Oct-Dec;21(2-4):260–267. doi: 10.1002/jnr.490210218. [DOI] [PubMed] [Google Scholar]
  3. Barnes D., Munro P. M., Youl B. D., Prineas J. W., McDonald W. I. The longstanding MS lesion. A quantitative MRI and electron microscopic study. Brain. 1991 Jun;114(Pt 3):1271–1280. doi: 10.1093/brain/114.3.1271. [DOI] [PubMed] [Google Scholar]
  4. Berneman A., Ternynck T., Avrameas S. Natural mouse IgG reacts with self antigens including molecules involved in the immune response. Eur J Immunol. 1992 Mar;22(3):625–633. doi: 10.1002/eji.1830220303. [DOI] [PubMed] [Google Scholar]
  5. Blakemore W. F. Demyelination of the superior cerebellar peduncle in the mouse induced by cuprizone. J Neurol Sci. 1973 Sep;20(1):63–72. doi: 10.1016/0022-510x(73)90118-4. [DOI] [PubMed] [Google Scholar]
  6. Blakemore W. F. Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone. J Neurol Sci. 1973 Sep;20(1):73–83. doi: 10.1016/0022-510x(73)90119-6. [DOI] [PubMed] [Google Scholar]
  7. Cook S. D., Troiano R., Rohowsky-Kochan C., Jotkowitz A., Bielory L., Mehta P. D., Oleske J., Bansil S., Dowling P. C. Intravenous gamma globulin in progressive MS. Acta Neurol Scand. 1992 Aug;86(2):171–175. doi: 10.1111/j.1600-0404.1992.tb05061.x. [DOI] [PubMed] [Google Scholar]
  8. Coutinho A. Beyond clonal selection and network. Immunol Rev. 1989 Aug;110:63–87. doi: 10.1111/j.1600-065x.1989.tb00027.x. [DOI] [PubMed] [Google Scholar]
  9. Goodkin D. E., Ransohoff R. M., Rudick R. A. Experimental therapies for multiple sclerosis: current status. Cleve Clin J Med. 1992 Jan-Feb;59(1):63–74. doi: 10.3949/ccjm.59.1.63. [DOI] [PubMed] [Google Scholar]
  10. Grundke-Iqbal I., Bornstein M. B. Multiple sclerosis: serum gamma globulin and demyelination in organ culture. Neurology. 1980 Jul;30(7 Pt 1):749–754. doi: 10.1212/wnl.30.7.749. [DOI] [PubMed] [Google Scholar]
  11. Kerlero de Rosbo N., Honegger P., Lassmann H., Matthieu J. M. Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein. J Neurochem. 1990 Aug;55(2):583–587. doi: 10.1111/j.1471-4159.1990.tb04173.x. [DOI] [PubMed] [Google Scholar]
  12. Ludwin S. K. Remyelination in the central nervous system and the peripheral nervous system. Adv Neurol. 1988;47:215–254. [PubMed] [Google Scholar]
  13. MILLER H. G., FOSTER J. B., NEWELL D. J., BARWICK D. D., BREWIS R. A. MULTIPLE SCLEROSIS: THERAPEUTIC TRIALS OF CHLOROQUINE, SOLUBLE ASPIRIN, AND GAMMAGLOBULIN. Br Med J. 1963 Dec 7;2(5370):1436–1439. doi: 10.1136/bmj.2.5370.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mastaglia F. L., Carroll W. M., Jennings A. R. Spinal cord lesions induced by antigalactocerebroside serum. Clin Exp Neurol. 1989;26:33–44. [PubMed] [Google Scholar]
  15. Matsiota P., Blancher A., Doyon B., Guilbert B., Clanet M., Kouvelas E. D., Avrameas S. Comparative study of natural autoantibodies in the serum and cerebrospinal fluid of normal individuals and patients with multiple sclerosis and other neurological diseases. Ann Inst Pasteur Immunol. 1988 Jan-Feb;139(1):99–108. doi: 10.1016/0769-2625(88)90134-1. [DOI] [PubMed] [Google Scholar]
  16. Moll C., Mourre C., Lazdunski M., Ulrich J. Increase of sodium channels in demyelinated lesions of multiple sclerosis. Brain Res. 1991 Aug 16;556(2):311–316. doi: 10.1016/0006-8993(91)90321-l. [DOI] [PubMed] [Google Scholar]
  17. Prineas J. W., Barnard R. O., Kwon E. E., Sharer L. R., Cho E. S. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol. 1993 Feb;33(2):137–151. doi: 10.1002/ana.410330203. [DOI] [PubMed] [Google Scholar]
  18. Prineas J. W., Barnard R. O., Kwon E. E., Sharer L. R., Cho E. S. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol. 1993 Feb;33(2):137–151. doi: 10.1002/ana.410330203. [DOI] [PubMed] [Google Scholar]
  19. Raine C. S., Diaz M., Pakingan M., Bornstein M. B. Antiserum-induced dissociation of myelinogenesis in vitro. An ultrastructural study. Lab Invest. 1978 Apr;38(4):397–403. [PubMed] [Google Scholar]
  20. Raine C. S., Moore G. R., Hintzen R., Traugott U. Induction of oligodendrocyte proliferation and remyelination after chronic demyelination. Relevance to multiple sclerosis. Lab Invest. 1988 Oct;59(4):467–476. [PubMed] [Google Scholar]
  21. Rodriguez M., Dunkel A. J., Thiemann R. L., Leibowitz J., Zijlstra M., Jaenisch R. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin. J Immunol. 1993 Jul 1;151(1):266–276. [PubMed] [Google Scholar]
  22. Rodriguez M. Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells. Lab Invest. 1991 Mar;64(3):358–370. [PubMed] [Google Scholar]
  23. Rodriguez M., Lennon V. A., Benveniste E. N., Merrill J. E. Remyelination by oligodendrocytes stimulated by antiserum to spinal cord. J Neuropathol Exp Neurol. 1987 Jan;46(1):84–95. doi: 10.1097/00005072-198701000-00008. [DOI] [PubMed] [Google Scholar]
  24. Rodriguez M., Lennon V. A. Immunoglobulins promote remyelination in the central nervous system. Ann Neurol. 1990 Jan;27(1):12–17. doi: 10.1002/ana.410270104. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez M., Scheithauer B. W., Forbes G., Kelly P. J. Oligodendrocyte injury is an early event in lesions of multiple sclerosis. Mayo Clin Proc. 1993 Jul;68(7):627–636. doi: 10.1016/s0025-6196(12)60597-7. [DOI] [PubMed] [Google Scholar]
  26. Rodriguez M., Scheithauer B. Ultrastructure of multiple sclerosis. Ultrastruct Pathol. 1994 Jan-Apr;18(1-2):3–13. doi: 10.3109/01913129409016267. [DOI] [PubMed] [Google Scholar]
  27. Roström B. Specificity of antibodies in oligoclonal bands in patients with multiple sclerosis and cerebrovascular disease. Acta Neurol Scand Suppl. 1981;86:1–84. [PubMed] [Google Scholar]
  28. Schuller E., Govaerts A. First results of immunotherapy with immunoglobulin G in multiple sclerosis patients. Eur Neurol. 1983;22(3):205–212. doi: 10.1159/000115560. [DOI] [PubMed] [Google Scholar]
  29. Soukop W., Tschabitscher H. Gammaglobulintherapie bei Multipler Sklerose (MS). Theoretische Uberlegungen und erste klinische Erfahrungen mit 7S-Immunglobulinen in der MS-Therapie. Wien Med Wochenschr. 1986 Sep 30;136(18):477–480. [PubMed] [Google Scholar]
  30. Tenser R. B., Hay K. A., Aberg J. A. Immunoglobulin G immunosuppression of multiple sclerosis. Suppression of all three major lymphocyte subsets. Arch Neurol. 1993 Apr;50(4):417–420. doi: 10.1001/archneur.1993.00540040069017. [DOI] [PubMed] [Google Scholar]
  31. Varela F. J., Coutinho A. Second generation immune networks. Immunol Today. 1991 May;12(5):159–166. doi: 10.1016/S0167-5699(05)80046-5. [DOI] [PubMed] [Google Scholar]
  32. Walsh M. J., Tourtellotte W. W. Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis. J Exp Med. 1986 Jan 1;163(1):41–53. doi: 10.1084/jem.163.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wiebe S., Lee D. H., Karlik S. J., Hopkins M., Vandervoort M. K., Wong C. J., Hewitt L., Rice G. P., Ebers G. C., Noseworthy J. H. Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis. Ann Neurol. 1992 Nov;32(5):643–650. doi: 10.1002/ana.410320507. [DOI] [PubMed] [Google Scholar]
  34. Yan J., Richert J. R., Sirdofsky M. D. High-dose intravenous immunoglobulin for multiple sclerosis. Lancet. 1990 Sep 15;336(8716):692–692. doi: 10.1016/0140-6736(90)92188-n. [DOI] [PubMed] [Google Scholar]
  35. van Engelen B. G., Hommes O. R., Pinckers A., Cruysberg J. R., Barkhof F., Rodriguez M. Improved vision after intravenous immunoglobulin in stable demyelinating optic neuritis. Ann Neurol. 1992 Dec;32(6):834–835. doi: 10.1002/ana.410320624. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES