alexa Identification of an autoantibody to vascular endothelial cell-specific antigens in patients with systemic vasculitis.


Journal of Kidney

Author(s): Brasile L, Kremer JM, Clarke JL, Cerilli J

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Abstract PURPOSE: Although immunologic mechanisms have been postulated in the pathogenesis of vasculitis, an autoimmune process directed against specific autologous vascular wall antigens has not been previously documented. We examined the role of an immunologic response to vascular endothelial cell (VEC) antigens in patients with vasculitis, because of the observed immunogenicity of VECs in renal and cardiac allograft recipients. PATIENTS AND METHODS: The study patients included 21 with systemic vasculitis and four with hypersensitivity vasculitis. A healthy, normal control group consisted of 51 young subjects and 61 older subjects. Thirty-two patients with connective tissue diseases were also evaluated. The presence of autoantibody to autologous monocytes and other cell types was determined with previously described standard crossmatch techniques. Patient sera exhibiting autoantibody to autologous monocytes were screened against a panel of allogeneic cells. The cell panel consisted of concordant T and B lymphocytes, monocytes, and VECs from 16 umbilical cord donors. Sera from four patients were analyzed for specificity to the vascular endothelium of frozen sections of vessels. RESULTS: An autoantibody to VEC antigens was detected in 18 of the 21 patients (86\%) with confirmed systemic vasculitis, not of the hypersensitivity type. This autoantibody was highly cytotoxic, complement-fixing, and specific for antigens on the surface of the VEC. Findings on allogeneic VEC panel analysis support the existence of multiple allotypes in the VEC antigen system. In three patients, fluctuations in the titer of the autoantibody generally correlated with clinical symptoms. In the four patients screened for the specificity of the autoantibody to anatomically different cadaveric blood vessels, specific anatomic patterns of reactivity were observed. Autoantibody to VEC antigens was not found in young controls and was documented in low frequency in older controls and in patients with connective tissue diseases. The autoantibody was seen in one of four patients (25\%) with hypersensitivity vasculitis. CONCLUSION: Our results indicate that an autoantibody to VEC antigens may be involved in the pathogenesis of systemic vasculitis or may be a diagnostic marker for the disease process.
This article was published in Am J Med and referenced in Journal of Kidney

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