Seizer Lennart, Gostner Johanna M, Garbers Christoph, Licht Melina, Sager Sebastian, Brandl Andreas, Schubert Christian
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Tübingen, Tübingen, Germany.
Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Medical University of Innsbruck, Innsbruck, Austria.
Front Immunol. 2025 May 8;16:1491475. doi: 10.3389/fimmu.2025.1491475. eCollection 2025.
Rheumatoid arthritis (RA) is a chronic autoimmune disease of mostly 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 59-year-old female RA patient collected her entire urine over 30 days in 12-h intervals (60 consecutive measurements in total). Subsequently, cortisol, interleukin-6 (IL-6), orosomucoid-2 (ORM-2), neopterin and creatinine 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 perceived pain, perceived RA disease activity and emotional states. Once a week, the patient was interviewed online and had an appointment with 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 IL-6 and urinary ORM-2 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, emotional states and body temperature, however, mirrored the course of the rheumatologic indices.
This integrative single-case study clearly demonstrated the importance of process analysis for the evaluation of therapeutic measures in RA. In the studied patient, urinary levels of neopterin, IL-6 and ORM-2 were not found to be appropriate biomarkers of short-term fluctuations in RA disease activity. Instead, the results reported by the patient proved to be a useful tool for ambulatory and longitudinal monitoring of RA.
类风湿关节炎(RA)是一种病因和病理生理学大多未知的慢性自身免疫性疾病。在这项针对一名类风湿关节炎患者的综合性单病例研究中,我们有独特的机会密切监测在自然发生的病情发作及随后药物变更期间内分泌、免疫和疾病变量的个体动态变化。
这位59岁的类风湿关节炎女性患者以12小时间隔在30天内收集了她的全部尿液(总共连续测量60次)。随后,测定尿液样本中的皮质醇、白细胞介素-6(IL-6)、类粘蛋白-2(ORM-2)、新蝶呤和肌酐水平。此外,患者每天早晚完成DIARI,这是一组关于诸如感知疼痛、感知类风湿关节炎疾病活动度和情绪状态等变量的问卷。患者每周接受一次在线访谈,并与她的风湿病学家预约,在预约中确定类风湿关节炎疾病活动度的几个指标:SDAI、CDAI和DAS28。从这些数据构建了各种时间序列用于统计分析。
在研究的前12天,类风湿关节炎疾病状态从低活动度增加到高活动度。随后,药物发生了变更,这被证明在降低类风湿关节炎疾病活动度方面是有效的。然而,尿新蝶呤水平、尿IL-6水平和尿ORM-2水平对疾病活动度的增加或药物变更均未显示出任何反应。然而,患者关于疼痛、类风湿关节炎疾病活动度、情绪状态和体温的每日报告反映了风湿病学指标的变化过程。
这项综合性单病例研究清楚地证明了过程分析在评估类风湿关节炎治疗措施中的重要性。在该研究患者中,未发现新蝶呤、IL-6和ORM-2的尿水平是类风湿关节炎疾病活动度短期波动的合适生物标志物。相反,患者报告的结果被证明是类风湿关节炎门诊和纵向监测的有用工具。