Modulation of MHC Expression on Human Endothelial Cells by Sera from Patients with Systemic Lupus Erythematosus

Abstract

Major histocompatibility complex (MHC) antigen expression on cells is a prerequisite for immune interaction with activated T-cells. This study examined the ability of sera from patients with systemic lupus erythematosus (SLE) to modulate MHC expression on vascular endothelial cells. SLE sera were able to selectively upregulate MHC class I antigen expression on cultured human umbilical venous endothelial (HUVE) cells, without concomitant induction of MHC class II antigen. The stimulation index (SI) for MHC class I expression produced by SLE sera (1.21 ± 0.23) was significantly higher than those for normal controls (1.01 ± 0.10) ( P < 0.0001) and non-SLE patients (1.12 ± 0.14) ( P < 0.05). Additionally, active SLE patients had higher mean SI than inactive patients ( P < 0.001). Preincubation of SLE sera with Protein A-Sepharose beads conjugated with antibodies against tumor necrosis factor-α and interferon-α was able to significantly reduce their ability to upregulate class I MHC expression by HUVE cells, indicating that these cytokines were responsible for the modulatory effect. This could be an important mechanism for the immune-mediated vascular injury seen in SLE.