The Role of Hepatitis Delta Virus in Sjogren's Syndrome

干燥综合征(SS)是一种病因不明的自身免疫性疾病。 它是第二种最常见的自身免疫性疾病，在 女性与女性的比例(9：1)。存在强有力的证据支持病毒 SS的病因，但到目前为止还没有直接的因果关系 已经成立了。我们的假设是不止一种病毒可能会引发 SS的发展概况。为了更好地了解唾液中存在的病毒 对于SS患者的腺体，我们使用定制的病毒微阵列芯片来鉴定病毒 SS患者和健康志愿者唾液腺的分布。使用这个 平台上，我们已经确定了一组明显的SS肝炎阳性患者 三角洲病毒(HDV)。我们的初步数据不仅揭示了 SS患者唾液腺中的HDV序列 存在HDV抗原。使这种病毒特征更加独特，这些患者 已检测出乙肝病毒抗原和抗体为阴性，这是唯一已知的 HDV的辅助病毒。本提案旨在定义HDV在SS和 确定以下表达式之间是否存在直接的因果关系 HDV抗原或基因组和唾液腺功能改变。体外研究 将评估HDV抗原或基因组表达和细胞 在唾液腺细胞系中发挥作用。接下来，体内研究将评估表达 小鼠唾液腺中的HDV抗原和基因组。对An的评估 在一个完整的系统中自主感染HDV将定义HDV 启动一种类似SS的表型。这笔赠款的第三个目标将提供一项测试，以检测 唾液腺组织中低水平HDV感染及鉴定 唾液腺中HDV水平与北京地区HDV水平的相关性 血清或唾液。唾液中HDV序列和抗原的鉴定 PSS患者的腺体是Sjögren‘s领域的重大发现 证候研究将对当前的治疗产生重大影响 治疗这种自身免疫性疾病的方法。

Sjögren's syndrome (SS) is an autoimmune disease of unknown etiology. It is the second most common autoimmune disease with predominance noted in females compared to makes (9:1). Strong evidence exists supporting a viral etiology of SS, but as of yet a direct cause and effect relationship has not been established. It is our hypothesis that more than one virus may be able to trigger the development of SS. To get a better picture of the viruses present in salivary glands of SS patients, we used a custom viral microarray chip to identify virus profiles in the salivary glands of SS patients and healthy volunteers. Using this platform, we have identified a distinct cohort of SS patients positive for Hepatitis Delta Virus (HDV). Our preliminary data has revealed not only the presence of HDV sequence in salivary glands of a subset of SS patients, but also the presence of HDV antigen. Making this viral profile more unique, these patients have tested negative for Hepatitis B virus antigen and antibody, the only known helper virus of HDV. This proposal aims to define the role of HDV in SS and determine if a direct cause-and-effect relationship exists between expression of the HDV antigen or genome and altered salivary gland function. In vitro studies will evaluate the impact of HDV antigen or genome expression and cellular function in salivary gland cell lines. Next, in vivo studies will evaluate expression of HDV antigen and genome in mouse salivary glands. Evaluation of an autonomous HDV infection in an intact system will define the ability of HDV to initiate a SS-like phenotype. The third aim of this grant will deliver a test to detect low-level HDV infection specifically in salivary gland tissue and identify correlations between levels of HDV in salivary gland and those identified in serum or saliva. Identification of HDV sequence and antigen in the salivary glands of pSS patients is a significant discovery in the field of Sjögren's syndrome research and stands to greatly impact the current therapeutic approaches used to treat this autoimmune disease.