Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Oct;70(1):74–83.

Brain-reactive autoantibody levels in the sera of ageing autoimmune mice.

S A Hoffman 1, D N Arbogast 1, P M Ford 1, D W Shucard 1, R J Harbeck 1
PMCID: PMC1542230  PMID: 3319304

Abstract

Brain-reactive autoantibodies are thought to play an important role in mediating central nervous system (CNS) disorders in systemic lupus erythematosus (SLE). In this paper the developmental occurrence of these antibodies in the sera of autoimmune mice, i.e. NZB, NZB/W, MRL/l and BXSB mice were examined. All murine strains tested, whether autoimmune or not, showed some degree of serum reactivity toward brain antigens. Autoimmune mice, however, displayed higher levels of serum brain-reactive antibodies, and at earlier ages, than non-autoimmune mice. Immunofluorescence assays against brain sections and adsorption assays, with both neural and non-neural tissue, indicated a heterogeneity in the specificity of the populations of brain-reactive antibodies present. These studies provide an important step in characterizing the appearance and diversity of brain-reactive autoantibodies, with the goal of better understanding their significance and potential role in mediating CNS dysfunction in SLE.

Full text

PDF
74

Images in this article

Selected References

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

  1. Aarli J. A., Fontana A. Immunological aspects of epilepsy. Epilepsia. 1980 Oct;21(5):451–457. doi: 10.1111/j.1528-1157.1980.tb04295.x. [DOI] [PubMed] [Google Scholar]
  2. Abel T., Gladman D. D., Urowitz M. B. Neuropsychiatric lupus. J Rheumatol. 1980 May-Jun;7(3):325–333. [PubMed] [Google Scholar]
  3. Alexander E. L., Murphy E. D., Roths J. B., Alexander G. E. Congenic autoimmune murine models of central nervous system disease in connective tissue disorders. Ann Neurol. 1983 Aug;14(2):242–248. doi: 10.1002/ana.410140211. [DOI] [PubMed] [Google Scholar]
  4. Bluestein H. G. Heterogeneous neurocytotoxic antibodies in systemic lupus erythematosus. Clin Exp Immunol. 1979 Feb;35(2):210–217. [PMC free article] [PubMed] [Google Scholar]
  5. Bluestein H. G. Neurocytotoxic antibodies in serum of patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3965–3969. doi: 10.1073/pnas.75.8.3965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bluestein H. G., Williams G. W., Steinberg A. D. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med. 1981 Feb;70(2):240–246. doi: 10.1016/0002-9343(81)90756-7. [DOI] [PubMed] [Google Scholar]
  7. Bluestein H. G., Zvaifler N. J. Brain-reactive lymphocytotoxic antibodies in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1976 Feb;57(2):509–516. doi: 10.1172/JCI108303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bresnihan B., Oliver M., Grigor R., Hughes G. R. Brain reactivity of lymphocytotoxic antibodies in systemic lupus erythematosus with and without cerebral involvement. Clin Exp Immunol. 1977 Dec;30(3):333–337. [PMC free article] [PubMed] [Google Scholar]
  9. Bresnihan B., Oliver M., Williams B., Hughes G. R. An antineuronal antibody cross-reacting with erythrocytes and lymphocytes in systemic lupus erythematosus. Arthritis Rheum. 1979 Apr;22(4):313–320. doi: 10.1002/art.1780220401. [DOI] [PubMed] [Google Scholar]
  10. Diederichsen H., Pyndt I. C. Antibodies against neurons in a patient with systemic lupus erythematosus, cerebral palsy, and epilepsy. Brain. 1970;93(2):407–412. doi: 10.1093/brain/93.2.407. [DOI] [PubMed] [Google Scholar]
  11. Feinglass E. J., Arnett F. C., Dorsch C. A., Zizic T. M., Stevens M. B. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore) 1976 Jul;55(4):323–339. doi: 10.1097/00005792-197607000-00004. [DOI] [PubMed] [Google Scholar]
  12. Harbeck R. J., Hoffman A. A., Hoffman S. A., Shucard D. W., Carr R. I. A naturally occurring antibody in New Zealand mice cytotoxic to dissociated cerebellar cells. Clin Exp Immunol. 1978 Feb;31(2):313–320. [PMC free article] [PubMed] [Google Scholar]
  13. Harbeck R. J., Hoffman A. A., Hoffman S. A., Shucard D. W. Cerebrospinal fluid and the choroid plexus during acute immune complex disease. Clin Immunol Immunopathol. 1979 Aug;13(4):413–425. doi: 10.1016/0090-1229(79)90083-7. [DOI] [PubMed] [Google Scholar]
  14. Hoffman S. A., Arbogast D. N., Day T. T., Shucard D. W., Harbeck R. J. Permeability of the blood cerebrospinal fluid barrier during acute immune complex disease. J Immunol. 1983 Apr;130(4):1695–1698. [PubMed] [Google Scholar]
  15. Hoffman S. A., Hoffman A. A., Shucard D. W., Harbeck R. J. Antibodies to dissociated cerebellar cells in New Zealand mice as demonstrated by immunofluorescence. Brain Res. 1978 Mar 10;142(3):477–486. doi: 10.1016/0006-8993(78)90910-1. [DOI] [PubMed] [Google Scholar]
  16. Hofstein R., Barnett B., Samuel D. The effect of anti-synaptosomal membrane antibodies of neurotransmitter uptake. J Neurochem. 1981 Jul;37(1):14–21. doi: 10.1111/j.1471-4159.1981.tb05285.x. [DOI] [PubMed] [Google Scholar]
  17. How A., Dent P. B., Liao S. K., Denburg J. A. Antineuronal antibodies in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 1985 Jul;28(7):789–795. doi: 10.1002/art.1780280710. [DOI] [PubMed] [Google Scholar]
  18. Johnson R. T., Richardson E. P. The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 1968 Jul;47(4):337–369. doi: 10.1097/00005792-196807000-00002. [DOI] [PubMed] [Google Scholar]
  19. Karpiak S. E., Huang Y. L., Rapport M. M. Immunological model of epilepsy. Epileptiform activity induced by fragments of antibody to GM1 ganglioside. J Neuroimmunol. 1982 Aug;3(1):15–21. doi: 10.1016/0165-5728(82)90014-5. [DOI] [PubMed] [Google Scholar]
  20. Kurki P., Helve T., Dahl D., Virtanen I. Neurofilament antibodies in systemic lupus erythematosus. J Rheumatol. 1986 Feb;13(1):69–73. [PubMed] [Google Scholar]
  21. Lal H., Bennett M., Bennett D., Forster M. J., Nandy K. Learning deficits occur in young mice following transfer of immunity from senescent mice. Life Sci. 1986 Aug 11;39(6):507–512. doi: 10.1016/0024-3205(86)90506-0. [DOI] [PubMed] [Google Scholar]
  22. Miovic M. L., Pizer L. I. Characterization of RNA synthesized in isolated nuclei of herpes simplex virus type 1-infected KB cells. J Virol. 1980 Jan;33(1):567–571. doi: 10.1128/jvi.33.1.567-571.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nandy K. Brain-reactive antibodies in mouse serum as a function of age. J Gerontol. 1972 Apr;27(2):173–177. doi: 10.1093/geronj/27.2.173. [DOI] [PubMed] [Google Scholar]
  24. Nandy K., Lal H., Bennett M., Bennett D. Correlation between a learning disorder and elevated brain-reactive antibodies in aged C57BL/6 and young NZB mice. Life Sci. 1983 Oct 10;33(15):1499–1503. doi: 10.1016/0024-3205(83)90853-6. [DOI] [PubMed] [Google Scholar]
  25. Rudick R. A., Eskin T. A. Neuropathological features of a lupus-like disorder in autoimmune mice. Ann Neurol. 1983 Sep;14(3):325–332. doi: 10.1002/ana.410140311. [DOI] [PubMed] [Google Scholar]
  26. Shirai T., Mellors R. C. Natural cytotoxic autoantibody against thymocytes in NZB mice. Clin Exp Immunol. 1972 Sep;12(1):133–152. [PMC free article] [PubMed] [Google Scholar]
  27. Theofilopoulos A. N., McConahey P. J., Izui S., Eisenberg R. A., Pereira A. B., Creighton W. D. A comparative immunologic analysis of several murine strains with autoimmune manifestations. Clin Immunol Immunopathol. 1980 Mar;15(3):258–278. doi: 10.1016/0090-1229(80)90039-2. [DOI] [PubMed] [Google Scholar]
  28. Toh B. h., Mackay I. R. Autoantibody to a novel neuronal antigen in systemic lupus erythematosus and in normal human sera. Clin Exp Immunol. 1981 Jun;44(3):555–559. [PMC free article] [PubMed] [Google Scholar]
  29. Williams C. A., Barna J., Schupf N. Antibody to Thy-1 antigen injected into rat hypothalamus selectively inhibits carbamyl choline induced drinking. Nature. 1980 Jan 3;283(5742):82–84. doi: 10.1038/283082a0. [DOI] [PubMed] [Google Scholar]
  30. Williams G. W., Bluestein H. G., Steinberg A. D. Brain-reactive lymphocytotoxic antibody in the cerebrospinal fluid of patients with systemic lupus erythematosus: correlation with central nervous system involvement. Clin Immunol Immunopathol. 1981 Jan;18(1):126–132. doi: 10.1016/0090-1229(81)90016-7. [DOI] [PubMed] [Google Scholar]
  31. Wilson H. A., Winfield J. B., Lahita R. G., Koffler D. Association of IgG anti-brain antibodies with central nervous system dysfunction in systemic lupus erythematosus. Arthritis Rheum. 1979 May;22(5):458–462. doi: 10.1002/art.1780220504. [DOI] [PubMed] [Google Scholar]
  32. Winfield J. B., Brunner C. M., Koffler D. Serologic studies in patients with systemic lupus erythematosus and central nervous system dysfunction. Arthritis Rheum. 1978 Apr;21(3):289–294. doi: 10.1002/art.1780210301. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES