Rheumatologische Schwerpunktpraxis Würzburg, Haugerpfarrgasse 7, 97070, Würzburg, Germany.
Department of Rheumatology, University Clinic Wuerzburg, Würzburg, Germany.
Clin Rheumatol. 2024 Aug;43(8):2445-2452. doi: 10.1007/s10067-024-07032-0. Epub 2024 Jun 14.
Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g., the cytokines driving inflammation. Obesity influences the course of RA, likely involving leptin; the exact mechanisms are not completely understood. This study investigates BMI influence on RA cytokine profiles and the possibility of predicting ACPA status and disease activity measured by Power-Doppler sonography (PDS).
Patients were examined using a multi-biomarker disease assay and PDS examination of wrists and MCP and PIP joints and stratified according to ACPA status and BMI, using prediction precision to determine BMI cutoff. Analysis was performed using elastic net regularization of logistic and multiple regression. We then attempted to predict ACPA status/PDS activity based on a bootstrap approach.
A total of 120 measurements from 95 patients were performed. ACPA status prediction peaked at BMI 26 kg/m, with AUC 0.82. PDS activity prediction had a mean average error of < 1.6 PDS points for all groups. In obese patients, cytokine profiles appear to align in ACPA-positive and -negative patients, with leptin playing a greater role in predicting PDS activity, but with some remaining differences.
When stratified according to BMI, cytokine patterns can predict ACPA status and PDS activity in RA with a high degree of precision. This indicates that studies into the pathophysiology of RA should take BMI into account, to differentiate between disease- and obesity-associated phenomena. The underlying pathological processes of ACPA-negative and -positive RA appear different. Multi-cytokine evaluations may provide a deeper understanding of disease processes. Key Points • A multi-cytokine approach combined with ultrasonography and modern mathematical methods can contribute to a deeper understanding of the relationship between systemic and joint inflammation. • BMI influences cytokine profiles in rheumatoid arthritis and appears to "override" disease-specific processes. • Using cytokines only, and adjusting for BMI, it is possible to predict the ACPA status and joint inflammation with considerable precision.
类风湿关节炎可根据 ACPA 和 RF 状态进行分类。ACPA 状态可能与其他病理生理差异相关，例如驱动炎症的细胞因子。肥胖影响 RA 的病程，可能涉及瘦素；确切的机制尚不完全清楚。本研究调查 BMI 对 RA 细胞因子谱的影响，以及预测 ACPA 状态和通过 Power-Doppler 超声 (PDS) 测量的疾病活动的可能性。
对患者进行多生物标志物疾病检测和 PDS 腕关节、MCP 和 PIP 关节检查，并根据 ACPA 状态和 BMI 进行分层，使用预测精度确定 BMI 截止值。使用逻辑和多元回归的弹性网络正则化进行分析。然后，我们试图基于引导方法预测 ACPA 状态/PDS 活性。
共对 95 例患者的 120 次测量进行了分析。ACPA 状态预测在 BMI 为 26kg/m 时达到峰值，AUC 为 0.82。所有组的 PDS 活性预测平均误差均<1.6 个 PDS 点。在肥胖患者中，ACPA 阳性和阴性患者的细胞因子谱似乎趋于一致，瘦素在预测 PDS 活性方面发挥更大作用，但仍存在一些差异。
当根据 BMI 分层时，细胞因子模式可以以很高的精度预测 RA 中的 ACPA 状态和 PDS 活性。这表明，RA 的病理生理学研究应考虑 BMI，以区分疾病相关和肥胖相关现象。ACPA 阴性和阳性 RA 的潜在病理过程不同。多细胞因子评估可能提供对疾病过程的更深入了解。关键点 • 多细胞因子方法结合超声检查和现代数学方法有助于更深入地了解系统性和关节炎症之间的关系。• BMI 影响类风湿关节炎中的细胞因子谱，并似乎“覆盖”疾病特异性过程。• 使用细胞因子并调整 BMI，可以相当精确地预测 ACPA 状态和关节炎症。
