Objective

To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function.

Design

We used baseline data from the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren–Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre.

Results

In 216 participants (mean age 66 years, mean BMI 27.3 kg/m², 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid.

Conclusions

Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity.

中文翻译：

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血脂与膝关节和手部骨关节炎严重程度的关联：IMI-APPROACH 队列

客观的

研究脂质组学特征与骨关节炎 (OA) 严重程度的关系，考虑膝关节和手部 OA、疼痛和功能的影像学结果。

设计

我们使用了来自应用公私研究支持骨关节炎临床进展 (APPROACH) 队列的基线数据，其中包括符合美国风湿病学会临床分类标准的膝关节 OA 患者。用 Kellgren-Lawrence 总分对 X 线膝关节和手部 OA 严重程度进行量化。使用经过验证的问卷评估膝关节和手部疼痛和功能。我们使用基于串联质谱 (LC-MS/MS) 平台的液相色谱法对空腹血浆高阶脂质和脂类进行量化。使用惩罚性线性回归，我们评估了脂质组学解释的 OA 严重程度的差异，并调整了临床协变量（年龄、性别、体重指数 (BMI) 和降脂药物）、测量批次和临床中心。

结果

在 216 名参与者（平均年龄 66 岁，平均 BMI 27.3 kg/m ²，75% 的女性）中，我们量化了 603 种高级脂质（三酰基甘油、二酰基甘油、胆固醇酯、神经酰胺、游离脂肪酸、鞘磷脂、磷脂）和 28 种磷脂。脂质组学分别解释了 3% 和 2% 的影像学膝关节和手部 OA 严重程度的差异。脂质与膝关节疼痛或功能无关。脂质组学分别占手部疼痛和功能差异的 12% 和 6%。研究的 OA 严重程度结果与结合和游离花生四烯酸、结合棕榈油酸、油酸、亚油酸和二十二碳五烯酸的脂质组学分数相关。

结论

在 APPROACH 队列中，脂质组学解释了 OA 严重程度变化的一小部分，这对于结果手部疼痛最为明显。我们的研究结果表明，类花生酸可能与 OA 的严重程度有关。