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Anti-endothelial cell antibodies in patients with cerebral small vessel disease
Akio Kimura1, Takeo Sakurai, Megumi Yamada
1Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, Japan. kimura1@gifu-u.ac.jp
Insights
High levels of anti-tropomyosin alpha-4 chain (TPM4) antibodies may contribute to cerebral small vessel disease (CSVD) in the elderly. This suggests an autoimmune link in CSVD pathogenesis.
Area of Science:
- Neurology
- Immunology
- Vascular Biology
Background:
- Cerebral small vessel disease (CSVD) pathogenesis in the elderly is not well understood.
- Endothelial cell activation and dysfunction are implicated in CSVD.
- Anti-endothelial cell antibodies (AECAs) are linked to endothelial dysfunction and inflammation.
Purpose of the Study:
- To investigate the association between AECAs and CSVD pathogenesis in the elderly.
- To identify specific AECAs and their target antigens in elderly CSVD patients.
Main Methods:
- Examined AECAs in sera from elderly subjects with and without CSVD, and healthy volunteers.
- Utilized 2D immunoblotting with human brain microvascular endothelial cells.
- Identified antibody target antigens using liquid chromatography-tandem mass spectrometry.
- Quantified anti-TPM4 antibody levels via ELISA.
Main Results:
- Four AECAs were frequently detected in elderly CSVD patients.
- Identified target antigens included tropomyosin alpha-4 chain (TPM4), vimentin, alpha-enolase, and annexin A2.
- Anti-TPM4 antibody was significantly more prevalent in CSVD patients.
- Elevated anti-TPM4 antibody levels were observed in elderly individuals with CSVD.
Conclusions:
- An autoimmune and inflammatory process involving high anti-TPM4 antibody levels may contribute to CSVD development in the elderly.
- Findings suggest anti-TPM4 antibodies as potential biomarkers or therapeutic targets for CSVD.
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.
