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

利用分子特征为干燥综合征提供个性化 B 细胞靶向治疗

• 批准号: MR/X004694/1
• 负责人: Coziana Ciurtin
• 金额: $ 28.88万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX004694%2F1
• 关键词: Harnessing; molecular; signatures; deliver; personalised

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

Sjogren综合征（SS）是一种持续/持久的疾病，其特征在于体内产生水分的腺体炎症。症状和症状范围从干燥，关节疼痛和疲劳影响几乎所有患者，到更具限制组的器官和系统的严重参与。 SS的原因仍然未知，但与免疫系统中的缺陷有关。我们的初步研究表明，在SS的成年人中，特殊类型的免疫细胞（称为B和T细胞）的表现更为异常，导致器官和组织损伤。我们想了解为什么在具有相同性别和年龄的SS和健康对照（HC）的成年人中，它们转录的免疫细胞和基因不同，并试图确定我们如何影响这些细胞的行为方式，这将为SS患者提供更好的治疗方法。为了研究这一点，我们与一家制药公司GSK建立了合作，该公司对患有SS患者进行了研究，并使用了两种靶向B细胞（称为利妥昔单抗和BelimumAb）的不同疗法进行治疗。他们仅使用这些治疗方法以及组合使用这些治疗方法，并比较了它们的效果与正常治疗方法（我们称为护理标准）。 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）对贝尔木单抗和利妥昔单抗反应反应的活性与控制良好的SS疾病（III）SS患者（通过查看B细胞靶向疗法/安慰剂后24周收集的样品，通过查看样品，Obigntive-2）.Obigntive-2：在反映疾病和唾液腺体的疾病中（综合疾病中的疾病）中的共享指纹和综合性疾病（组合），该疾病的共同反应（组合）构成了GORS的疾病。 GSK试验结束时B细胞靶向疗法

项目成果

POS0453 EXPLORATORY IMMUNOPHENOTYPE OF THE RARE DISEASE JUVENILE SJÖGREN'S SYNDROME REVEALS A DYSREGULATION OF B AND T MEMORY CELL FREQUENCIES

POS0453 罕见疾病青少年 SJäGren 综合征的探索性免疫表型揭示了 B 和 T 记忆细胞频率的失调

• DOI: 10.1136/annrheumdis-2022-eular.1082
• 发表时间: 2022
• 期刊: Annals of the Rheumatic Diseases
• 影响因子: 27.4
• 作者: Martin-Gutierrez L

Treatment strategies for Sjögren's syndrome with childhood onset: a systematic review of the literature.

• DOI: 10.1093/rheumatology/keab579
• 发表时间: 2022-03-02
• 期刊: Rheumatology (Oxford, England)
• 作者: Doolan G;Faizal NM;Foley C;Al-Obaidi M;Jury EC;Price E;Ramanan AV;Lieberman SM;Ciurtin C
• 通讯作者: Ciurtin C

Multi-Omic Biomarkers for Patient Stratification in Sjogren's Syndrome-A Review of the Literature.

• DOI: 10.3390/biomedicines10081773
• 发表时间: 2022-07-22
• 期刊: Biomedicines
• 影响因子: 4.7