Harnessing molecular signatures to deliver personalised B-cell targeted therapies in Sjogren's syndrome

干燥综合征（SS）是一种持续/长期的疾病，其特征是体内产生水分的腺体发炎。症状和体征包括干燥、关节疼痛和疲劳，几乎所有患者都会受到影响，但在少数患者中，器官和系统会严重受累。SS的病因尚不清楚，但与免疫系统缺陷有关。我们的初步研究表明，特殊类型的免疫细胞，称为B细胞和T细胞，在患有SS的成年人中表现得更加异常，导致器官和组织损伤。我们想知道他们为什么免疫细胞和基因转录是不同的在成人SS和健康对照组(HC)相同的性别与年龄,并试图确定如何影响这些细胞的行为方式,这将有望带来更好的治疗SS患者。能看看这个,我们建立了一个与制药公司合作,葛兰素史克,运行一个研究SS患者和治疗用两种不同的治疗目标B细胞,叫做利妥昔单抗和贝利单抗。他们单独使用这些治疗方法以及联合使用这些治疗方法，并比较它们与正常治疗（我们称之为标准治疗）的效果。除了评估患者的反应外，他们还收集了血液样本和唾液腺活检（在显微镜下切除小块组织以帮助诊断SS）。我们的研究目标是什么？目的-1：定义与患者血细胞转录的基因相关的指纹图谱，以寻找：(i) SS疾病与健康对照之间的差异；（ii）活动性SS疾病与控制良好的SS疾病（iii）对Belimumab和Rituximab有反应的SS患者与无反应的SS患者（通过观察基线与b细胞靶向治疗/安慰剂后24周收集的样本）。目标-2：在血液和唾液腺组织之间建立共享指纹，反映疾病活动性（结合GSK试验和UCL队列的患者）和GSK试验结束时对B细胞靶向治疗的潜在反应

Sjogren Syndrome (SS) is a persistent/long-lasting disease characterised by inflammation of the glands that produce moisture in the body. The signs and symptoms range from dryness, joint pain and fatigue affecting nearly all patients, to severe involvement of organs and systems, in a more limited group. The cause of SS remains unknown but is associated with defects in the immune system. Our preliminary research showed that specialised types of immune cells, called B and T cells behave more abnormally in adults with SS contributing to organ and tissue damage. We want to understand why immune cells and genes they transcribe are different in adults with SS and healthy controls (HC) of the same sex and age, and try to identify how we can influence the way these cells behave, which will hopefully lead to better treatments for patients with SS. To be able to look into this, we established a collaboration with a pharmaceutical company, GSK, who run a study in patients with SS and treated them with two different therapies which target B cells, called Rituximab and Belimumab. They used these treatments alone as well as in combination and compared how effective they are versus normal treatment (which we call standard of care). In addition to assessing patient response, they collected blood samples and also salivary gland biopsies (small pieces of tissue removed to view under the microscope to help diagnosing SS).What are our research aims?Objective-1: Define the fingerprints associated with the genes that are transcribed by patients blood cells to look for differences between :(i) SS disease vs. healthy controls; (ii) SS disease which is active versus well controlled (iii) SS patients who responded to Belimumab and Rituximab versus non-responders (by looking at samples collected at baseline vs 24 weeks post B-cell targeting therapies/placebo).Objective-2: Establish shared fingerprints between blood and salivary gland tissue that reflect disease activity (combining patients from the GSK trial and UCL cohorts) and potential response to B cell targeted therapies at the end of the the GSK trial