Cytotoxicity of sera from patients with scleroderma

Abstract

Sera from patients with progressive systemic sclerosis were compared with sera from normal individuals and from patients with other connective tissue diseases for cytotoxic effects on cultured human cells. More than 40% of the sera from patients with active progressive systemic sclerosis were cytotoxic by several criteria for pulmonary arterial or umbilical venous endothelial cells, foreskin fibroblasts, and neuroblastoma cells. Cytotoxic sera caused morphologic changes, uptake of trypan blue dye, and a decrease in the incorporation of 'H-thymidine into DNA. In contrast, only 4 sera from normal individuals or patients with other rheumatic diseases affected cell morphology, staining, or uptake of 3H-thymidine. Partial characterization of the cytotoxic factor indicated that it is sensitive to proteolysis by trypsin. The molecular weight of the factor was estimated to be similar to that of albumin.Progressive systemic sclerosis (PSS), or scleroderma, is characterized by alterations in connective tissue composition of skin and visceral organs, but the ~

Anti-endothelial cell antibodies in systemic sclerosis

“…This led to the hypothesis that a serum factor might induce vascular damage. Studies in the 1980s focused on various effects of SSc sera on cell cultures,59 60 61 62 63 64 65 and the observed prevalence of SSc sera cytotoxicity ranged from 19% to 75%. Some of these studies61 62 64 demonstrated antibody-dependent cell cytotoxicity mediated by SSc sera on various EC substrates, a mechanism also described in SLE66 and in WG 67.…”

“…Some authors assumed the cytotoxic factor in SSc serum to be a protease 59 68. This hypothesis remains interesting because further research69 demonstrated the presence of a 60 kDa granzyme in SSc sera, inducing profound EC growth inhibition while having a mitogenic effect on fibroblasts.…”

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis

“…Since then these antibodies have been described in a variety of connective tissue disease (Shingu & Hurd, 1981;Cohen, Johnson & Hurd, 1983;LeRoux et al, 1986;Baguley & Hughes, 1987;Hashemi, Smith & Izaguirre, 1987;Rosenbaum et al, 1988) and in association with vasculitis (Leung et al, 1986a(Leung et al, , 1986bBrasile et al, 1989;Heurkens et al, 1989;Ferraro et ai, 1990). Work in our laboratory and those of several other authors has shown that binding of AECA to endothelial cells is mediated by the F(ab')2 portion and not the Fc portion (Hashemi et al, 1987;Rosenbaum et al, 1988;Baguley & Hughes, 1989;Heurkens et al, 1989).…”

The Vascular Endothelium in Scleroderma

“…The activity was disease specific in some reports, while other reports described its presence in a small number of patients with other connective tissue diseases. The activity was reported to be the size of albumin, 40-SO kD in one report [68], as well as a SO00 dalton fraction in another study [70]. Some of the apparent confusion regarding endothelial cytotoxicity may involve methodologic differences, source of endothelial cells, and patient selection.…”