Endocrine, immune, and disease dynamics in a patient with rheumatoid arthritis during flare and medication change

Lennart Seizer, Johanna Gostner, Christoph Garbers, Melina Licht, Sebastian Sager, Christian Schubert
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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease of widely unknown etiology and pathophysiology. In this integrative single-case study on a patient with RA, we had the unique opportunity to closely monitor the individual dynamics of endocrine, immune and disease variables during a naturally occurring flare-up and subsequent medication change. The female RA patient collected her entire urine over 30 days in 12-h intervals (60 consecutive measurements in total). Subsequently, interleukin-6 (IL-6), orosomucoid-2, cortisol (ELISA), neopterin and creatinine (HPLC) levels were determined in the urine samples. Further, each morning and evening, the patient completed the DIARI, a set of questionnaires on variables such as subjective pain, subjective RA disease activity and emotional states. Once a week, besides an online video interview, the patient had an appointment at her rheumatologist, in which several indices of RA disease activity were determined: SDAI, CDAI and DAS28. From these data various time series were constructed for statistical analysis. RA disease state increased from low to high activity during the first 12 study days. Thereupon, the medication was changed, which proved effective in reducing RA disease activity. However, the levels of urinary neopterin, urinary orosomucoid-2 and urinary IL-6 did not show any response, neither to the increasing disease activity nor the medication change. The patient's daily reports on pain, RA disease activity and emotional states, however, mirrored the course of the rheumatologic indices. For the patient studied, urinary neopterin, urinary orosomucoid-2 and urinary IL-6 levels did not represent adequate biomarkers of short-term variations in RA disease activity. Patient-reported outcomes on the other hand might be a useful tool in the ambulatory and longitudinal monitoring of RA.
一名类风湿关节炎患者在病情发作和换药期间的内分泌、免疫和疾病动态变化
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其病因和病理生理学广为人知。在这项针对一名类风湿关节炎患者的单病例综合研究中,我们获得了一个独特的机会,可以在自然发作和随后换药期间密切监测内分泌、免疫和疾病变量的个体动态变化。这名女性 RA 患者在 30 天内以 12 小时为间隔收集了全部尿液(共连续测量 60 次)。随后,测定了尿样中的白细胞介素-6(IL-6)、类橙皮甙-2、皮质醇(ELISA)、新蝶呤和肌酐(HPLC)水平。此外,患者每天早晚都要填写 DIARI 问卷,这是一套关于主观疼痛、主观 RA 疾病活动和情绪状态等变量的问卷。除了在线视频访谈外,患者每周还去看一次风湿免疫科医生,医生会在访谈中确定几种 RA 疾病活动指数:SDAI、CDAI 和 DAS28。根据这些数据构建了各种时间序列,用于统计分析。在最初的 12 天研究中,RA 的疾病状态从低活动度上升到高活动度。随后,医生更换了药物,事实证明这有效降低了 RA 的疾病活动度。然而,尿液中的蝶呤、尿液中的类橙皮苷-2 和尿液中的 IL-6 水平并未显示出任何反应,无论是对疾病活动度的增加还是药物的改变都是如此。然而,患者每天关于疼痛、RA 疾病活动和情绪状态的报告反映了风湿病学指标的变化过程。对于所研究的患者来说,尿蝶呤、尿卵清蛋白-2 和尿 IL-6 水平并不能充分反映 RA 疾病活动的短期变化。另一方面,患者报告的结果可能是对 RA 进行动态和纵向监测的有用工具。
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