Anti-Endothelial Cell Antibodies in Patients with Cerebral Small Vessel Disease

Akio      Kimura; Takeo      Sakurai; Megumi      Yamada; Akihiro      Koumura; Yuichi      Hayashi; Yuji      Tanaka; Isao      Hozumi; Hirofumi      Ohtaki; Mitsuhiro      Chousa; Masao      Takemura; Mitsuru      Seishima; Takashi      Inuzuka

Abstract

The pathogenesis of cerebral small vessel disease (CSVD) in the elderly is poorly understood. Endothelial cell activation and dysfunction may play a causal role in the pathogenesis of CSVD. It was reported that anti-endothelial cell antibodies (AECAs) are associated with endothelial cell dysfunction and inflammation. We hypothesized that AECAs may be associated with the pathogenesis of CSVD. We examined AECAs in sera from 12 elderly subjects with CSVD, 12 elderly subjects without CSVD, and 18 healthy volunteers by 2-dimensional immunoblotting using primary cultured human brain microvascular endothelial cells as the antigen source. We identified 4 AECAs that were detected in sera from more than one-half of the elderly subjects with CSVD. Subsequently, we analyzed the target antigens of these 4 antibodies by liquid chromatography-tandem mass spectrometry. The target antigens of these 4 antibodies were tropomyosin alpha-4 chain (TPM4), vimentin, alpha-enolase, and annexin A2. Among these 4 antibodies, the anti-TPM4 antibody was significantly more frequently detected in sera from the elderly subjects with CSVD than the other subjects. We determined the anti-TPM4 antibody level in sera from 21 elderly subjects with CSVD and 25 subjects without CSVD by enzyme-linked immunosorbent assay. The anti-TPM4 antibody level was significantly higher in the subjects with than without CSVD. Therefore, an autoimmune, inflammatory process with high levels of anti-TPM4 antibody may contribute to the development of CSVD in the elderly.

Keywords: Autoantibody, endothelial cells, tropomyosin, white matter hyperintensity, (CSVD), AECAs, (MRI), Endothelial cell, ischemic infarcts, Geriatrics