M. Damianovich et al., PATHOGENIC ROLE OF ANTIENDOTHELIAL CELL ANTIBODIES IN VASCULITIS - ANIDIOTYPIC EXPERIMENTAL-MODEL, The Journal of immunology, 156(12), 1996, pp. 4946-4951
Idiotypic manipulation of naive mice has previously been used for indu
ction 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 vas
culitis in a murine model, AECA were derived from a Wegener's granulom
atosis patient's plasma. IgG was purified by absorption on a proteinas
e-3 affinity column resulting in the depletion of anti-neutrophil cyto
plasmic Ab activity. The absorbed IgG fraction displayed a high titer
of AECA as evidenced by a cyto-ELISA against unfixed human umbilical v
ein endothelial cells, BALB/c mice were actively immunized with the pu
rified AECA. Three months after a boost injection with the human AECA,
mice developed endogenous AECA (Ab3), but not Abs to proteinase-3, ca
rdiolipin, or DNA. Histologic examination of lungs and kidneys reveale
d both lymphoid cell infiltration surrounding arterioles and venules a
s well as deposition of Igs at the outer part of blood vessel walls. T
his experimental animal model of vasculitis, a product of our method o
f idiotypic manipulation, provides the first direct proof for the path
ogenicity of AECA.