Laboratory of Immunology, Institute of Biomedicine of Seville, IBiS, UGC Clinical Laboratories, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
Hospital Universitari Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
Clin Sci (Lond). 2019 Apr 29;133(8):997-1010. doi: 10.1042/CS20190111. Print 2019 Apr 30.
The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive combined antiretroviral therapy (cART). Integrated data from nuclear magnetic resonance (NMR)-based lipoprotein profiles, mass spectrometry (MS)-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune recovery status after 96 weeks of suppressive cART. The metabolomic signature of ART-naïve HIV subjects with a subsequent late immune recovery is the expression of pro-inflammatory molecules and glutaminolysis, which is likely related to elevate T-cell turnover in these patients. The knowledge about how these metabolic pathways are interconnected and regulated provides new targets for future therapeutic interventions not only in HIV infection but also in other metabolic disorders such as human cancers where glutaminolysis is the alternative pathway for energy production in tumor cells to meet their requirement of rapid proliferation.
与免疫恢复不良相关的免疫学、生物化学和分子机制还远未被人们所了解，而代谢组学分析为传统的可溶性标志物提供了额外的价值。在这里，我们提出了新的相关数据，这些数据可能有助于更好地理解在抑制性联合抗逆转录病毒治疗（cART）下，出现不一致反应和 HIV 进展之前的分子机制。基于核磁共振（NMR）的脂蛋白谱、基于质谱（MS）的代谢组学和可溶性血浆生物标志物的综合数据有助于构建预后和免疫进展工具，这些工具能够根据 HIV 感染者在接受抑制性 cART 96 周后的免疫恢复情况对其进行区分。在接受 ART 治疗的 HIV 感染者中，随后出现免疫恢复延迟的患者的代谢组学特征是促炎分子和谷氨酰胺分解的表达，这可能与这些患者 T 细胞更新增加有关。了解这些代谢途径是如何相互关联和调节的，为未来的治疗干预提供了新的靶点，不仅在 HIV 感染方面，而且在其他代谢紊乱方面，如人类癌症，谷氨酰胺分解是肿瘤细胞产生能量的替代途径，以满足其快速增殖的需求。
