ABERRANT EXPRESSION OF MEMBRANE COFACTOR PROTEIN AND DECAY-ACCELERATING FACTOR IN THE ENDOTHELIUM OF PATIENTS WITH SYSTEMIC-SCLEROSIS - A POSSIBLE MECHANISM OF VASCULAR DAMAGE

BACKGROUND: One of the main features of systemic sclerosis (SSc) is va scular damage, the mechanism of which is not understood. The aim of th is study was to investigate if complement (C) regulatory molecules, me mbrane cofactor protein (MCP), decay-accelerating factor (DAF), and CD 59, which normally protect endothelial cells from damage by autologous C, are absent or downregulated in vascular endothelium of patients wi th SSc. A deficiency or persistent down-regulation of the above molecu les is likely to render vascular endothelium of these patients suscept ible to damage by physiologically or pathologically activated C. From this point of view, expression of MCP, DAF, and CD59 was tested on end othelium of skin of normal subjects and patients with diffuse and limi ted forms of SSc. EXPERIMENTAL DESIGN: Punch biopsies of normal skin ( N = 11) and lesional and non-lesional skin of patients with diffuse (N = 5) and limited (N = 5) forms of SSc were obtained and serial sectio ns prepared. Immunoperoxidase staining of these sections was carried o ut using four monoclonal antibodies (MoAbs) directed to different epit opes of DAF, four to different epitopes of MCP, one to CD59 and one to von Willebrand factor. von Willebrand factor served as a marker of en dothelial cells. Besides normal skin, lesional skin of systemic lupus erythematosus and several inflammatory and proliferative diseases, des cribed below, served as controls. RESULTS: The endothelium of normal s kin strongly expressed all the three proteins. However, the endotheliu m of lesional and nonlesional skin of all the 10 patients with diffuse or limited forms of the disease tested, expressed either decreased or undetectable amounts of MCP and DAF. CD59 expression was normal in so me patients and lower than normal in others. Aberrant expression of MC P, DAF, or CD59 was not found in other control inflammatory, connectiv e tissue and proliferative diseases studied. CONCLUSIONS: In view of t he common function of MCP and DAF to protect self cells from autologou s C, their decrease or virtual absence from the endothelium of patient s with SSc strongly suggests that this deficiency may contribute to va scular damage, resulting in intima proliferation and, finally, fibrosi s.