Abstract

Anti-endothelial cell antibodies (AECA) are frequently detected in patients with systemic lupus erythematosus (SLE), but their pathological role remains unclear. We recently developed a solubilized cell surface protein capture enzyme-linked immunosorbent assay (CSP-ELISA) to detect antibodies against membrane proteins involved in autoimmune reactions. In this study, sera from 51 patients with biopsy-proven lupus nephritis (LN), 25 with SLE without renal involvement (non-LN SLE), 42 disease control (DC) subjects, and 80 healthy control (HC) subjects were tested for IgG- and IgA-AECA for human umbilical vein endothelial cells (HUVEC) and human glomerular EC (HGEC) by using CSP-ELISA. IgG- and IgA-AECA titers were significantly higher in LN and non-LN SLE patients than in the DC or HC (P < 0.001) groups. IgG- and IgA-AECA titers for HUVEC corresponded well with those for HGEC. The IgA-AECA level correlated with the SLE disease activity index and with histological evidence of active lesions (cellular proliferations, hyaline thrombi and wire loops, leukocytic infiltration, and fibrinoid necrosis) in LN patients (P < 0.001). The sensitivity of IgA-AECA as a diagnostic test for histological evidence of active lesions in LN patients was 0.92, with a specificity of 0.70. The significant correlation of IgA-AECA with glomerular hypercellularity indicates that IgA-AECA are associated with endothelial damage in LN.

Highlights

  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting various tissues, with diverse clinical manifestations accompanied by the presence of numerous autoantibodies

  • We evaluated the role of IgG and IgA isotypes of Anti-endothelial cell antibodies (AECA) to human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells (HGEC) in the diagnosis of SLE, and their association with clinical features and disease activity, using CSP-ELISA

  • All optical density (OD) 492 values were converted into arbitrary units (AU) by extrapolation from a standard curve shown in S1 Fig. Sera were considered positive for IgG- and IgA-AECA to HUVEC if the AU value was higher than 0.0299 and 0.252, respectively

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Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting various tissues, with diverse clinical manifestations accompanied by the presence of numerous autoantibodies. The role of IgA-AECA in SLE has not been well described, IgA-AECA may play an important role in LN as anti-DNA IgG and anti-DNA IgA is associated with both LN and active disease [15,16,17]. We evaluated the role of IgG and IgA isotypes of AECA to HUVEC and human glomerular endothelial cells (HGEC) in the diagnosis of SLE, and their association with clinical features and disease activity, using CSP-ELISA

Materials and Methods
Evaluation of disease activities
Results
Discussion
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