Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI

Abstract

The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) may be related to autoantibody-mediated neural dysfunction, vasculopathy and coagulopathy. We encountered an NPSLE patient whose brain showed characteristic diffuse symmetrical hyperintensity lesions in the cerebral white matter, cerebellum and middle cerebellar peduncles on T2-weighted magnetic resonance (MR) images. In this study, we investigated all the antigens that reacted strongly with autoantibodies in this patient's serum by two-dimensional electrophoresis (2DE), followed by western blotting (WB) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using rat brain proteins as the antigen source. As a result, we identified four antigens as beta-actin, alpha-internexin, 60 kDa heat-shock protein (Hsp60) and glial fibrillary acidic protein (GFAP). There are several reports on the detection of anti-endothelial cell antibodies (AECAs) in an SLE patients. Recently, one of the antigens reacting with AECAs in SLE patient's sera has been identified as human Hsp60. We speculated that the abnormal findings on brain MR images of our patient may be due to impairment of microcirculation associated with vascular endothelial cell injury mediated by the antibody against Hsp60. This proteomic analysis is a useful tool for identifying autoantigens in autoimmune diseases involving autoantibodies.