The oRAcle Study - Predicting the risk of infection in RA

类风湿性关节炎（RA）是一种长期的、无法治愈的疾病，影响了1%的成年人。它会导致关节疼痛和僵硬，久而久之会导致损伤。在类风湿性关节炎中，身体的免疫系统（用来防御感染的）变得过于活跃，错误地攻击身体自身的组织。治疗类风湿性关节炎的药物疗法是通过靶向免疫系统来实现的。这些药物被称为改善疾病的抗风湿药（DMARDs）。问题：类风湿性关节炎患者经常受到严重感染，入院人数是正常人的两倍。严重感染只是冰山一角，每年有超过30%的患者报告非严重感染。当病人感染时，他们的临床医生会停止他们的DMARDs。如果不治疗类风湿性关节炎，疾病活动会恶化，疾病可能会“爆发”。中断治疗方案与疾病恶化和关节损伤增加有关。研究问题目前认为，类风湿性关节炎患者感染风险的增加是药物治疗的副作用。然而，我们认为RA的活跃炎症过程是感染易感性的重要原因。我们认为这是因为慢性炎症矛盾地抑制了免疫系统，使患者面临更大的感染风险。临床经验支持了这一点，即疾病越严重的患者感染越多。目前尚不清楚疾病状态对人体抵抗感染的能力有多大影响。我们想要回答这个问题。研究目的我们的研究将探讨疾病状态对感染易感性的影响程度。我们的目标是研究一大群RA患者的临床和实验室特征，以确定哪些特征使他们在独立于药物治疗的情况下具有最大的感染风险。TACERA （Towards A Cure in RA）数据集已经获得了270名新诊断为RA的患者在开始治疗前的广泛临床信息和血液样本。它是近年来生成的最丰富的数据集之一，结合了大量的临床和实验室数据。重要的是，这是“真实生活”的数据，因为患者的治疗方式与常规临床实践一样。在整个研究过程中，所有的感染事件都被捕捉到了，因此已经确定了高风险群体。在这项研究中，我们将比较感染过的患者和没有感染过的患者。初步工作将确定其临床特征（如年龄、吸烟情况、疾病严重程度）的任何差异。TACERA数据集在开始使用dmard之前对患者的血液样本进行了详细的分析，测量了数千种控制免疫系统功能的基因的表达。我们可以看看这些数据，看看在感染的病人和没有感染的病人之间是否有什么具体的区别。这将有助于确定与感染风险相关的模式。然后，我们将研究dmard启动后血液中的变化，以确定与感染风险增加相关的免疫系统变化。我们将把这些模式与治疗开始前的模式进行比较。这将使我们能够评估药物和疾病对感染风险的相对贡献。研究影响：我们期望能够将血液检测结果与临床特征相结合，以确定每位患者发生感染的风险。这项测试可能有助于评分系统，考虑到感染的其他危险因素，并可能与许多炎症性疾病的患者有关。在临床实践中，这意味着我们可以识别高风险患者并对其进行个性化护理，预防感染，提高治疗安全性，并优化长期结果。

The backgroundRheumatoid Arthritis (RA) is a long-term, incurable condition, affecting 1% of the adult population. It causes joint pain and stiffness, which overtime can result in damage. In RA the body's immune system (which is designed to defend against infection) becomes too active and mistakenly attacks the body's own tissue. Drug therapies that treat RA do so by targeting the immune system. These are called disease-modifying antirheumatic drugs (DMARDs). The problemPatients with RA experience frequent and severe infections, with twice as many hospital admissions compared to people without the disease. Serious infections are the tip of the iceberg, with over 30% of patients reporting non-serious infections each year. When a patient has an infection, their clinician will stop their DMARDs. Without treatment for RA, disease activity worsens and the disease may 'flare'. Interrupted treatment regimens are associated worsening disease and increased joint damage. The research questionCurrent belief is that the increased risk of infection in patients with RA is a side effect of drug therapy. However, we propose that the active inflammatory process in RA is an important cause of susceptibility to infection. We believe that this is because chronic inflammation paradoxically suppresses the immune system, putting patients at greater risk of infection. This is supported by clinical experience where patients with more severe disease experience more infections. It is currently not known how much the disease state contributes to the body's ability to resist infection. We want to answer this question.Study aimOur research will address how much the disease state contributes to infection susceptibility. Our goal is to study the clinical and laboratory features of a large group of RA patients to identify which of these characteristics put them at greatest risk of infection, independent of drug therapy. Study planThe TACERA (Towards A Cure in RA) dataset has acquired extensive clinical information and blood samples on 270 patients with newly diagnosed RA prior to starting treatment. It is one of the richest datasets generated in recent years combining large amounts of clinical and laboratory data. Importantly, this is "real life" data because patients were treated as they would be in routine clinical practice. All infectious events have been captured throughout the study, and so the high risk group has already been identified. In this study we will compare the patients who have had an infection with those who did not. Initial work will identify any differences in their clinical characteristics (e.g. age, smoking, disease severity). The TACERA dataset has detailed analysis of the patients' blood samples prior to starting DMARDs, with the measurements of the expression of thousands of genes that control the way the immune system functions. We can look at this data and see if there are any specific differences between patients that developed infections compared to those who did not. This will help identify patterns associated with the risk of infection. We will then investigate changes in the blood after starting DMARDs, to identify changes in the immune system associated with an increased risk of infection. We will compare these patterns to those seen before therapy was started. This will enable us to assess the relative contribution of the drug and the disease on the risk of infection.Study impactWe anticipate being in a position to use a combination of blood test results with clinical features to determine for every patient their risk of developing an infection. This test may contribute to a scoring system that considers other risks factors for infection, and may be relevant to patients with many inflammatory disorders. In clinical practice this means we could identify high risk patients and personalise their care, preventing infection, improving safety of treatment, and optimising long-term outcomes.