Table_4_Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression.docx

PurposeNon-operative management of trapeziometacarpal osteoarthritis (TMOA) demonstrates only short-term symptomatic alleviation, and no approved disease modifying drugs exist to treat this condition. A key issue in these patients is that radiographic disease severity can be discordant with patient reported pain, illustrating the need to identify molecular mediators of disease. This study characterizes the biochemical profile of TMOA patients to elucidate molecular mechanisms driving TMOA progression.
MethodsPlasma from patients with symptomatic TMOA undergoing surgical (n=39) or non-surgical management (n=44) with 1-year post-surgical follow-up were compared using a targeted panel of 27 cytokines. Radiographic (Eaton-Littler), anthropometric, longitudinal pain (VAS, TASD, quick DASH) and functional (key pinch, grip strength) data were used to evaluate relationships between structure, pain, and systemic cytokine expression. Principal Component Analysis was used to identify clusters of patients.
ResultsPatients undergoing surgery had greater BMI as well as higher baseline quick DASH, TASD scores. Systemically, these patients could only be distinguished by differing levels of Interleukin-7 (IL-7), with an adjusted odds ratio of 0.22 for surgery for those with increased levels of this cytokine. Interestingly, PCA analysis of all patients (regardless of surgical status) identified a subset of patients with an “inflammatory” phenotype, as defined by a unique molecular signature consisting of thirteen cytokines.
ConclusionOverall, this study demonstrated that circulating cytokines are capable of distinguishing TMOA disease severity, and identified IL-7 as a target capable of differentiating disease severity with higher levels associated with a decreased likelihood of TMOA needing surgical intervention. It also identified a cluster of patients who segregate based on a molecular signature of select cytokines.

研究目的 腕掌关节骨关节炎（trapeziometacarpal osteoarthritis, TMOA）的非手术治疗仅能实现短期症状缓解，目前尚无获批的疾病修饰性药物用于该病症的治疗。此类患者的核心临床问题在于，影像学评估的疾病严重程度与患者自述的疼痛程度常存在不一致，这凸显了挖掘该疾病分子介导因子的必要性。本研究旨在解析腕掌关节骨关节炎患者的生化特征，以阐明驱动该疾病进展的分子机制。
研究方法 本研究纳入有症状的腕掌关节骨关节炎患者，其中接受手术治疗者39例、非手术治疗者44例，且手术患者均完成术后1年随访。研究采用靶向27种细胞因子的检测面板对患者血浆样本进行对比分析。同时收集患者的影像学（伊顿-利特尔分级，Eaton-Littler）、人体测量学、纵向疼痛评分（视觉模拟评分法Visual Analogue Scale, VAS、多伦多腕关节评分TASD、快速上肢功能障碍量表quick DASH）以及功能指标（捏力、握力）数据，以评估病变结构、疼痛症状与系统性细胞因子表达之间的关联。此外，采用主成分分析（Principal Component Analysis, PCA）识别患者聚类簇。
研究结果 接受手术治疗的患者基线BMI更高，且快速DASH评分、TASD评分也更高。系统性细胞因子分析显示，仅白细胞介素-7（Interleukin-7, IL-7）的水平差异可区分两类患者，该细胞因子水平升高者接受手术治疗的校正比值比为0.22。值得注意的是，对所有患者（无论是否接受手术）的主成分分析结果显示，存在一类“炎症表型”的患者亚群，其特征为包含13种细胞因子的独特分子特征谱。
研究结论 本研究整体表明，循环细胞因子可用于区分腕掌关节骨关节炎的疾病严重程度，并确定白细胞介素-7可作为区分疾病严重程度的标志物，其水平升高与TMOA患者需要手术干预的概率降低相关。此外，本研究还识别出一类可通过特定细胞因子分子特征进行聚类的患者亚群。