脑小血管病以复发性脑卒中和认知功能障碍为主要临床表现，但病因至今不明。我们发现脑小血管病患者外周血存在抗髓鞘抗原及抗神经抗原的自身反应性CD4+T细胞，因此我们推测反复出现的脑梗死引起脑内神经元、髓鞘的自身免疫反应，加重白质损伤、从而导致了认知功能的下降。本研究致力于脑小血管病的免疫机制研究：1）明确脑小血管病脑内及外周的自身免疫反应特征、以及与疾病复发和认知功能下降的关系；2）研究脑小血管病出现自身免疫反应的机制；3）探索通过免疫干预改善脑小血管病预后的策略。该研究结果将有助于揭示自身免疫反应在脑小血管病模型中的作用，增加我们对于该病发病机制的理解；通过特异性免疫干预可能改善脑小血管病的短期临床治疗效果和长期预后，并为脑小血管病导致的血管性认知障碍的治疗提供新的方向。

Cerebral small vessel disease (CSVD) is one of the main causes of recurrent stroke and vascular dementia with unknown pathogenesis. Antibodies and autoreactive CD4+T cells against brain antigens are found in the peripheral blood of CSVD patients. Based on these findings, our central hypothesis is that recurrent stroke induced the activation of CD4+ T cells and autoimmune response, facilitating white matter abnormalities and behavioral impairments. The overall goal of this proposal is to determine the genesis of autoimmunity in cerebral small vessel disease and explore its clinical relevance. Our specific aims are to: 1) determine the features of autoimmunity in cerebral small vessel disease; 2) investigate the mechanism of autoimmune response in cerebral small vessel disease; 3) whether autoimmunity contribute to cognitive decline and recurrence of stroke in patients with cerebral small vessel disease. The outcome of this proposal will provide a better understanding of the autoimmunity feature and mechanism after cerebral small vessel disease.