William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London EC1M 6BQ, UK.
Biomolecules. 2022 Feb 23;12(3):353. doi: 10.3390/biom12030353.
A precision medicine approach is widely acknowledged to yield more effective therapeutic strategies in the treatment of patients with chronic inflammatory conditions than the prescriptive paradigm currently utilized in the management and treatment of these patients. This is because such an approach will take into consideration relevant factors including the likelihood that a patient will respond to given therapeutics based on their disease phenotype. Unfortunately, the application of this precision medicine paradigm in the daily treatment of patients has been greatly hampered by the lack of robust biomarkers, in particular biomarkers for determining early treatment responsiveness. Lipid mediators are central in the regulation of host immune responses during both the initiation and resolution of inflammation. Amongst lipid mediators, the specialized pro-resolving mediators (SPM) govern immune cells to promote the resolution of inflammation. These autacoids are produced via the stereoselective conversion of essential fatty acids to yield molecules that are dynamically regulated during inflammation and exert potent immunoregulatory activities. Furthermore, there is an increasing appreciation for the role that these mediators play in conveying the biological actions of several anti-inflammatory therapeutics, including statins and aspirin. Identification and quantitation of these mediators has traditionally been achieved using hyphenated mass spectrometric techniques, primarily liquid-chromatography tandem mass spectrometry. Recent advances in the field of chromatography and mass spectrometry have increased both the robustness and the sensitivity of this approach and its potential deployment for routine clinical diagnostics. In the present review, we explore the evidence supporting a role for specific SPM as potential biomarkers for patient stratification in distinct disease settings together with methodologies employed in the identification and quantitation of these autacoids.
精准医学方法被广泛认为比目前用于治疗这些患者的规范治疗方法更能为慢性炎症患者提供有效的治疗策略。这是因为这种方法将考虑相关因素，包括患者基于疾病表型对特定治疗方法的反应可能性。不幸的是，由于缺乏强大的生物标志物，特别是用于确定早期治疗反应的生物标志物，这种精准医学方法在患者的日常治疗中的应用受到了极大的阻碍。脂质介质在炎症的启动和消退过程中对宿主免疫反应的调节中起着核心作用。在脂质介质中，专门的促解决介质（SPM）调节免疫细胞以促进炎症的消退。这些自体活性物质是通过必需脂肪酸的立体选择性转化产生的，在炎症过程中这些分子被动态调节，并发挥强大的免疫调节作用。此外，人们越来越认识到这些介质在传递几种抗炎治疗药物（包括他汀类药物和阿司匹林）的生物学作用方面的作用。这些介质的鉴定和定量传统上是使用带质谱联用技术，主要是液相色谱串联质谱法来实现的。色谱和质谱领域的最新进展提高了这种方法的稳健性和敏感性，使其有可能用于常规临床诊断。在本综述中，我们探讨了特定 SPM 作为特定疾病情况下患者分层的潜在生物标志物的证据，以及用于鉴定和定量这些自体活性物质的方法。
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