Anti-Endothelial Cell Antibodies (AECA) in Systemic Sclerosis - Increased Sensitivity using Different Endothelial Cell Substrates and Association with Other Autoantibodies

Abstract

Objective: One of the main features of systemic sclerosis (SSc) is vascular damage, the mechanism of which is not understood. In the present study we examined whether screening of SSc patients for different anti-endothelial cells antibodies (AECA) of various origins increase the sensitivity of AECA detection in SSc patients. Secondary aim was an attempt to correlate AECA with other common autoantibodies.

Materials & methods: 478 SSc patients were studied for the presence AECA. anti-cardiolipin (aCL), anti-dsDNA, anti-heparin (AHA), anti-pyruvate dehydrogenase (PDH) and anti-PDC-E2 autoantibodies. AECA levels were determined using human umbilical vein EC (HUVEC), bone marrow EC (BMEC), EC hybridoma (EA.hy 926) and Kaposi sarcoma EC (KS).

Results: Positive AECA were found in 49.5% of SSc patients (27.1% HUVEC: 34.3% BMEC; 26.3% EaHy 926 and 22.7% KS). The highest percent reactivity of AECA was obtained using microvascular BMEC. When combining BMEC and either other cell lines the reactivity ranged from 41.4% to 46%. A significant association between AECA on the one hand and AHA (p<0.001) and anti-PDH (p<0.05) on the other was seen. Cross-reactivity with anti-PDC-E2 was excluded by inhibition tests, but AHA and anti-PDH may be part of the spectrum of AECA.

Conclusions: Since false-negative AECA may result from lack of expression of various antigens on a specific EC, analysis of AECA in SSc patients requires using several EC types, including microvascular EC.

Key Words:

• Anti-endothelial cell antibodies
• autoantibodies
• pyruvate dehydrogenase
• systemic sclerosis
• vasculitis