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. 1986 Oct;78(4):865–869. doi: 10.1172/JCI112672

Antibodies to neurofilament protein in retinitis pigmentosa.

G M Galbraith, D Emerson, H H Fudenberg, C J Gibbs, D C Gajdusek
PMCID: PMC423702  PMID: 3093532

Abstract

Antibodies reactive with heterologous neural tissue were detected by indirect immunofluorescence microscopy in the sera of 17 of 34 patients with retinitis pigmentosa, one of 30 normal control sera, and a variable percentage of sera derived from subjects with diverse ocular and neurological diseases. These antibodies were also found both in disease-free first degree relatives and in spouses of patients with retinitis pigmentosa. Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human spinal cord components followed by immunoblots with sera under study revealed that the serum antibody was specific for the high molecular weight protein subunit of neurofilaments. No correlation was found between the presence of these antibodies and other immunological and clinical parameters in retinitis pigmentosa. These findings suggest that release of piled-up neurofilaments from damaged neurones in retinitis pigmentosa triggers B lymphocytes autoreactive to neurofilament antigens.

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Selected References

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  1. Aoki T., Gibbs C. J., Jr, Sotelo J., Gajdusek D. C. Heterogeneic autoantibody against neurofilament protein in the sera of animals with experimental kuru and Creutzfeldt-Jakob disease and natural scrapie infection. Infect Immun. 1982 Oct;38(1):316–324. doi: 10.1128/iai.38.1.316-324.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bahmanyar S., Liem R. K., Griffin J. W., Gajdusek D. C. Characterization of antineurofilament autoantibodies in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol. 1984 Jul;43(4):369–375. doi: 10.1097/00005072-198407000-00002. [DOI] [PubMed] [Google Scholar]
  3. Boughman J. A., Conneally P. M., Nance W. E. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980 Mar;32(2):223–235. [PMC free article] [PubMed] [Google Scholar]
  4. Brinkman C. J., Pinckers A. J., Broekhuyse R. M. Immune reactivity to different retinal antigens in patients suffering from retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1980 Jul;19(7):743–750. [PubMed] [Google Scholar]
  5. Dräger U. C., Hofbauer A. Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina. Nature. 1984 Jun 14;309(5969):624–626. doi: 10.1038/309624a0. [DOI] [PubMed] [Google Scholar]
  6. Gajdusek D. C. Hypothesis: interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system. N Engl J Med. 1985 Mar 14;312(11):714–719. doi: 10.1056/NEJM198503143121110. [DOI] [PubMed] [Google Scholar]
  7. Galbraith G. M., Fudenberg H. H. One subset of patients with retinitis pigmentosa has immunologic defects. Clin Immunol Immunopathol. 1984 May;31(2):254–260. doi: 10.1016/0090-1229(84)90245-9. [DOI] [PubMed] [Google Scholar]
  8. Hogan R. N., Baringer J. R., Prusiner S. B. Progressive retinal degeneration in scrapie-infected hamsters: a light and electron microscopic analysis. Lab Invest. 1981 Jan;44(1):34–42. [PubMed] [Google Scholar]
  9. Hooks J. J., Detrick-Hooks B., Geis S., Newsome D. A. Retinitis pigmentosa associated with a defect in the production of interferon-gamma. Am J Ophthalmol. 1983 Dec;96(6):755–758. doi: 10.1016/s0002-9394(14)71920-8. [DOI] [PubMed] [Google Scholar]
  10. Kaufmann E., Geisler N., Weber K. SDS-PAGE strongly overestimates the molecular masses of the neurofilament proteins. FEBS Lett. 1984 May 7;170(1):81–84. doi: 10.1016/0014-5793(84)81373-3. [DOI] [PubMed] [Google Scholar]
  11. Kurki P., Helve T., Virtanen I. Antibodies to cytoplasmic intermediate filaments in rheumatic diseases. J Rheumatol. 1983 Aug;10(4):558–562. [PubMed] [Google Scholar]
  12. Kurki P., Miettinen A., Salaspuro M., Virtanen I., Stenman S. Cytoskeleton antibodies in chronic active hepatitis, primary biliary cirrhosis, and alcoholic liver disease. Hepatology. 1983 May-Jun;3(3):297–302. doi: 10.1002/hep.1840030304. [DOI] [PubMed] [Google Scholar]
  13. Kurki P., Virtanen I. The detection of human antibodies against cytoskeletal components. J Immunol Methods. 1984 Mar 16;67(2):209–223. doi: 10.1016/0022-1759(84)90462-9. [DOI] [PubMed] [Google Scholar]
  14. LUNA L. G. FURTHER STUDIES OF BODIAN'S TECHNIQUE; WITH SPECIAL EMPHASIS ON THE IMPREGNATING AND REDUCING SOLUTIONS. Am J Med Technol. 1964 Nov-Dec;30:355–362. [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Liem R. Simultaneous separation and purification of neurofilament and glial filament proteins from brain. J Neurochem. 1982 Jan;38(1):142–150. doi: 10.1111/j.1471-4159.1982.tb10865.x. [DOI] [PubMed] [Google Scholar]
  17. Linder E., Kurki P., Andersson L. C. Autoantibody to "intermediate filament" in infectious mononucleosis. Clin Immunol Immunopathol. 1979 Dec;14(4):411–417. doi: 10.1016/0090-1229(79)90093-x. [DOI] [PubMed] [Google Scholar]
  18. Merril C. R., Goldman D., Sedman S. A., Ebert M. H. Ultrasensitive stain for proteins in polyacrylamide gels shows regional variation in cerebrospinal fluid proteins. Science. 1981 Mar 27;211(4489):1437–1438. doi: 10.1126/science.6162199. [DOI] [PubMed] [Google Scholar]
  19. Osung O. A., Chandra M., Holborow E. J. Antibody to intermediate filaments of the cytoskeleton. Ann Rheum Dis. 1982 Feb;41(1):69–73. doi: 10.1136/ard.41.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sotelo J., Gibbs C. J., Jr, Gajdusek D. C. Autoantibodies against axonal neurofilaments in patients with Kuru and Creutzfeldt-Jakob disease. Science. 1980 Oct 10;210(4466):190–193. doi: 10.1126/science.6997994. [DOI] [PubMed] [Google Scholar]
  21. Stefansson K., Marton L. S., Dieperink M. E., Molnar G. K., Schlaepfer W. W., Helgason C. M. Circulating autoantibodies to the 200,000-dalton protein of neurofilaments in the serum of healthy individuals. Science. 1985 May 31;228(4703):1117–1119. doi: 10.1126/science.4039466. [DOI] [PubMed] [Google Scholar]
  22. Toh B. H., Gibbs C. J., Jr, Gajdusek D. C., Goudsmit J., Dahl D. The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases. Proc Natl Acad Sci U S A. 1985 May;82(10):3485–3489. doi: 10.1073/pnas.82.10.3485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Toh B. H., Gibbs C. J., Jr, Gajdusek D. C., Tuthill D. D., Dahl D. The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from chimpanzees with kuru or Creutzfeldt-Jakob disease; a 62-kDa neurofilament-associated protein reacts with sera from sheep with natural scrapie. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3894–3896. doi: 10.1073/pnas.82.11.3894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Toh B. H., Yildiz A., Sotelo J., Osung O., Holborow E. J., Kanakoudi F., Small J. V. Viral infections and IgM autoantibodies to cytoplasmic intermediate filaments. Clin Exp Immunol. 1979 Jul;37(1):76–82. [PMC free article] [PubMed] [Google Scholar]
  25. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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