CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice

Alla Akkerman, Weiqing Huang, Xiaobo Wang, Meera Ramanujam, Lena Schiffer, Michael P. Madaio, Stephen M. Factor, Anne Davidson

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

NZW "x" BXSB F1 mice develop SLE that is associated with an anti-phospholipid syndrome characterized by anti-cardiolipin antibodies, thrombocytopenia and small coronary artery thrombosis. This syndrome is immune mediated and, dependent, on CD4+T cells. To determine whether disease in these mice can be treated with blockade of T cell costimulation we treated them with the CD28 antagonist CTLA4Ig at 9 or 12 weeks of age. CTLA4Ig completely prevented both SLE nephritis and myocardial infarcts if it was given at 9 weeks of age, before anti-cardiolipin antibodies could be detected in the serum and prevented both B cell expansion and activation and the development of peripheral monocytosis. If treatment was delayed until 12 weeks of age after cardiolipin antibodies had arisen but before the onset of clinical disease, CTLA4Ig had very little effect on disease progression. These findings indicate that CD4+T cell activation through CD28 is critical for disease initiation in this model but plays little role in disease progression or tissue damage. These findings have relevance to the treatment of anti-phospholipid syndrome in humans.

Original languageEnglish (US)
Pages (from-to)445-451
Number of pages7
JournalAutoimmunity
Volume37
Issue number6-7
DOIs
StatePublished - Sep 1 2004

Keywords

  • Anti-phospholipid syndrome
  • CTLA4Ig
  • NZW/BXSB mice
  • SLE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Akkerman, A., Huang, W., Wang, X., Ramanujam, M., Schiffer, L., Madaio, M. P., Factor, S. M., & Davidson, A. (2004). CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice. Autoimmunity, 37(6-7), 445-451. https://doi.org/10.1080/08916930400008524