Idiotypic manipulation of naive mice has previously been used for Induction of systemic autoimmune diseases (eg. anti phospholipid syndrome, systemic lupus erythematosus, Wagoner's granulomatosis). The aim of this study focused on'the utilization of this technique to induce the production of antiendothelial cells antibodies (AECA) and autoimmune vasculitls in a murine model. AECA were derived from a Wagoner's granulomatosis patient plasma. IgG was purified by absorption on a proteinase-3 affinity column resulting In the depletion of antl-neutrophll cytoplasmic antibody activity. The absorbed IgG fraction displayed a high tiler of AECA as evidenced by a cyto-ELISA against unfixed HUVEC. 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 antibodies to proteinase-3. cardiolipln or DMA Histological examination of lungs and kidneys revealed both lymphoid cell Infiltration surrounding arterloles and venules as well as deposition of immunoglobulins at the outer part of blood vessel walls. This experimental animal model of vasculitis, a product of our method of Idiotypic manipulation, has provided the first direct proof for the pathogenicity of AECA.
|Journal||Human Antibodies and Hybridomas|
|Publication status||Published - 1996|
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