Inhibition of diabetes in NOD mice by idiotypic induction of SLE

I. Krause, Y. Tomer, D. Elias, M. Blank, B. Gilburd, I. R. Cohen, Y. Shoenfeld

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The present study was undertaken to investigate whether active induction of systemic lupus erythematosus (SLE) in non-obese diabetic (NOD) mice could affect their development of insulin-dependent diabetes mellitus (IDDM). NOD mice were immunized with a human IgM mAb carrying the 16/6 idiotype (MIV-7) or with control human IgM. The mice were bled monthly and tested for SLE- associated autoantibodies in the serum and for the presence of leukopenia, thrombocytopenia, proteinuria and immunoglobulin deposits in the kidneys. The development of diabetes was determined by a blood glucose level exceeding 15 mM on two consecutive weekly determinations and by the presence of insulitis in the pancreas. The NOD mice immunized with MIV-7 developed high and persistent levels of autoantibodies, including anti-DNA, anti-histones and anti-cardiolipin, untreated mice and those immunized with normal human IgM did not produce these autoantibodies. The MIV-7-immunized mice also manifested an elevated erythrocyte sedimentation rate, leukopenia, thrombocytopenia and significant proteinuria, as well as deposits of Ig in their kidney glomeruli. Thus, NOD mice immunized with MIV-7 developed both autoantibodies and clinical features of SLE. The MIV-7-treated mice, however, showed a significantly lower incidence of IDDM (25% vs. 90%, P<0.003), accompanied by amelioration of the insulitis. The present study indicates that the induction of SLE by idiotypic immunization can protect NOD mice from developing IDDM, pointing to the importance of immune dysregulation in shift from one autoimmune disease to another.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalJournal of Autoimmunity
Volume13
Issue number1
DOIs
StatePublished - Aug 1999
Externally publishedYes

Keywords

  • Autoantibodies
  • Diabetes
  • Idiotypes
  • NOD
  • SLE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Krause, I., Tomer, Y., Elias, D., Blank, M., Gilburd, B., Cohen, I. R., & Shoenfeld, Y. (1999). Inhibition of diabetes in NOD mice by idiotypic induction of SLE. Journal of Autoimmunity, 13(1), 49-55. https://doi.org/10.1006/jaut.1999.0292