IN-VITRO CYTOTOXICITY OF IGG ANTIBODIES ON VASCULAR ENDOTHELIAL-CELLSFROM PATIENTS WITH ENDEMIC PERIPHERAL VASCULAR-DISEASE IN TAIWAN

A unique peripheral vascular disorder called 'blackfoot disease' is en demic in a limited area on the south-west coast of Taiwan. Clinically, the signs and symptoms of blackfoot disease (BFD) are similar to thos e of arteriosclerosis and Buerger's disease. A destruction of vascular endothelial cells (ECs) takes place at an early stage in the affected limbs. Currently, the cause of BFD is believed to be artesian drinkin g water containing a high concentration of arsenic and/or humic substa nces, although the mechanism of EC destruction is not entirely underst ood. The purpose of the present study was to examine the factors relat ed to EC damage in BFD. Thus, we investigated the effects of purified IgG collected from patients with BFD (BFD-IgG) and from normal control s (N-IgG) on cultured EC. We found that: (1) EC binding activity of BF D-IgG was significantly higher than that of N-IgG; (2) BFD-IgG, at a c oncentration higher than 100 mu g/ml but not N-IgG, induced concentrat ion-dependent EC cytotoxicity; (3) BFD-IgG at a concentration of 100 m u g/ml stimulated neither the release of von Willebrand factor nor the expression of intercellular adhesion molecule-1 by EC. Fluorescent vi deo microscopic examination revealed an increase in transcapillary and interstitial diffusion of nailfold capillary loops in clinically norm al fingers of BFD patients. These findings strongly suggested that imm unological mechanisms played a significant role in the pathogenesis of BFD. We propose that only persons who produce the IgG anti-endothelia l cell antibody are potential victims of BFD. (C) 1998 Elsevier Scienc e Ireland Ltd. All rights reserved.