Abstract
Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood–brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient’s serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was integrated with cDNA identical to EphB2, which plays critical roles in neuronal cells and endothelial cells. HUVECs and human brain microvascular endothelial cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody may define a novel group of brain disorders. Anti-EphB2 antibody can interfere not only with endothelial cells including those of the BBB (acting as an anti-endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal antibody) if the BBB has been breached. Future studies should determine the clinical prevalence and specificity of anti-EphB2 antibody, and the molecular mechanisms by which anti-EphB2 antibody mediates neuronal and vascular pathological lesions.
Highlights
A group of brain disorders involving autoantibodies targeting cell-surface or synaptic proteins has been identified
Thediagnosis is based on the topographic distribution and evolution of symmetric lesions visualized by computed tomography (CT) and magnetic resonance imaging (MRI) in the bilateral thalami and other specific brain areas [2]
Using SARF, we successfully identified ephrin type B receptor 2 (EphB2), which has critical functions in neuronal and endothelial cells (ECs) [6], as a target of autoantibody from a patient with Acute necrotizing encephalopathy (ANE) complicated with systemic lupus erythematosus (SLE)
Summary
A group of brain disorders involving autoantibodies targeting cell-surface or synaptic proteins has been identified. Autoantibodies cause tissue damage through a number of mechanisms. Cell-surface target antigens are susceptible to disruption by autoantibodies, and syndromes mediated by these autoantibodies often mimic animal models with genetic or pharmacological disruption of these molecules [1]. Thediagnosis is based on the topographic distribution and evolution of symmetric lesions visualized by computed tomography (CT) and magnetic resonance imaging (MRI) in the bilateral thalami and other specific brain areas [2]. The pathogenesis remained obscure, vasculopathy with breakdown of the blood–brain barrier (BBB) was suggested [3]
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