Pathogenic role of anti-endothelial cell antibodies in vasculitis: An idiotypic experimental model

Maya Damianovich, Boris Gilburd, Jacob George, Nicoletta Del Papa, Arnon Afek, Iris Goldberg, Yuri Kopolovic, Daniel Roth, Gad Barkai, Pier Luigi Meroni, Yehuda Shoenfeld

Research output: Contribution to journalArticlepeer-review

Abstract

Idiotypic manipulation of naive mice has previously been used for induction of systemic autoimmune diseases (e.g., antiphospholipid syndrome, systemic lupus erythematosus, and Wegener's granulomatosis). The aim of this study focused on the utilization of this technique to induce the production of anti-endothelial cells Abs (AECA) and autoimmune vasculitis in a murine model. AECA were derived from a Wegener's granulomatosis patient's plasma. IgG was purified by absorption on a proteinase-3 affinity column resulting in the depletion of anti-neutrophil cytoplasmic Ab activity. The absorbed IgG fraction displayed a high tiler of AECA as evidenced by a cyto-ELISA against unfixed human umbilical vein endothelial cells. BALB/c mice were actively immunized with the purified AECA. Three months after a boost injection with the human AECA, mice developed endogenous AECA (Ab3), but not Abs to proteinase-3, cardiolipin, or DNA. Histologic examination of lungs and kidneys revealed both lymphoid cell infiltration surrounding arterioles and venules as well as deposition of Igs at the outer part of blood vessel walls. This experimental animal model of vasculitis, a product of our method of idiotypic manipulation, provides the first direct proof for the pathogenicity of AECA.

Original languageEnglish
Pages (from-to)4946-4951
Number of pages6
JournalJournal of Immunology
Volume156
Issue number12
Publication statusPublished - Jun 15 1996

ASJC Scopus subject areas

  • Immunology

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