IgG4与泪腺良性淋巴上皮病变发病关系的研究

Benign lymphoepithelial lesion (BLEL) of lacrimal gland is a kind of eye disease which always recurs and has poor curative effect. So far, it is still not clear about the specific etiology and pathogenesis of BLEL of lacrimal gland. It has been suggested through existing researches that lgG4 is closely related to the pathogenesis of BLEL of lacrimal gland, but the mechanism of action of lgG4 has not been reported. Through our study in advance, we found that lgG4 may participate in the pathogenesis of lacrimal idiopathic orbital inflammatory pseudotumor through Primary immunodeficiency pathway, TCR pathway and BCR pathway. Therefore, according to the researches of others and our study in advance, we propose a hypothesis that "IgG4 concentration increasing may be the key factor of pathogenesis of BLEL of lacrimal gland, and it probably have closed relationship to three pathways above". On the basis of our early experiment, we would like to increase the number of sample to do some systemic researches about the relationship between IgG4 and BLEL of lacrimal gland, as well as the research of mechanism that IgG4 causes BLEL of lacrimal gland attack. This study is expected to contribute to some new clinical diagnosis evidence as well as new experimental data of pathogenesis of BLEL of lacrimal gland.

泪腺良性淋巴上皮病变（benign lymphoepithelial lesion,BLEL）是一种反复发作、治疗效果欠佳的眼科疾病。迄今，泪腺BLEL的具体病因和发病机制尚不清楚。已有研究提示lgG4与泪腺BLEL的发生密切相关，但有关lgG4的作用机制未见报道。我们课题组先期实验显示lgG4可能通过Primary immunodeficiency、TCR和BCR三条信号通路参与了泪腺型炎性假瘤的发病过程。为此，基于他人研究成果以及结合我们现有实验结果，提出"IgG4升高可能是泪腺BLEL发病的关键性因素，其致病可能与上述三条信号通路相关"的假说。本课题将在先期研究基础上，扩大样本量来系统研究IgG4与泪腺BLEL发病之间的关系，以及研究IgG4导致泪腺BLEL发生的作用机制。研究结果以期为泪腺BLEL提供新的临床诊断指标，同时也为其发生机制提供新的实验依据。

泪腺良性淋巴上皮病变（Lacrimal gland benign lymphoepithelial lesion, LGBLEL）以双侧或单侧泪腺弥漫性无痛性肿大和眼睑肿胀为主要眼部病变的疾病。本课题主要对LGBLEL的病因及发病机制进行了研究，并取得以下结果：（1）收集经过病理组织学检查确诊为LGBLEL患者病变泪腺组织及血样标本总计达103例，建立了标本量最多的LGBLEL标本库，为LGBLEL的研究奠定了基础；（2）完成LGBLEL患者血清中IgG4的检测，结果显示LGBLEL患者血清IgG4含量升高阳性率为54.3%，提示血清IgG4检测可以为LGBLEL患者的诊断提供一定参考依据；（3）完成LGBLEL患者泪腺标本中IgG4蛋白表达的检测，结果显示LGBLEL病变泪腺组织中IgG4免疫组化染色阳性率为90%，提示IgG4与LGBLEL的发生有关；（4）完成LGBLEL组与对照组患者病变组织标本的基因芯片检测，结果显示有32条信号通路表达显著上调，25条信号通路表达下调。（5）完成LGBLEL组与对照组患者TCR通路的验证，结果显示TCR通路参与了LGBLEL的病变过程；（6）完成LGBLEL组与对照组患者BCR通路的验证，结果提示BCR通路可能参与了LGBLEL的发病过程。（7）完成LGBLEL组与对照组患者Primary immunodeficiency通路的验证，结果显示Primary immunodeficiency通路参与了LGBLEL的发病过程。