PDF(Pubmed)
Abstract：
Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs. Growth differential factor-15 (GDF-15) is a transforming growth factor-β (TGF-β) family member known to regulate several biological processes involved in cell aging and stress responses. Since PLWH exhibit premature aging and metabolic dysregulation, here we measured the plasma levels of GDF-15 by ELISA and metabolic proteins by proteomic array and correlated the results with clinical parameters in ART-controlled PLWH (including INRs and IRs) and healthy subjects (HS). We found that GDF-15 levels were significantly elevated in PLWH compared to HS. GDF-15 levels were positively correlated with age and negatively associated with body mass and LDL cholesterol levels in the study subjects. Also, elevated GDF-15 levels were correlated with differential dysregulation of multiple metabolic proteins in PLWH. These results suggest that GDF-15 protein may serve as a biomarker of metabolic dysregulation and aging, and this biomarker will be useful in clinical trials targeting aging and metabolic disorders in ART-treated PLWH.
摘要：
尽管通过抗逆转录病毒疗法（ART）有效控制了HIV的复制，相当数量的HIV感染者(PLWH)未能实现完全免疫重建,因此被视为免疫无反应者(INRs).与恢复CD4T细胞数量和功能的免疫应答者（IRs）相比，来自这些INR的CD4T细胞表现出突出的线粒体功能障碍和过早衰老，这在增加非艾滋病的发病率中起着重要作用，非传染性疾病。迄今为止,没有可靠的生物标志物可以用来表征和管理PLWH，尤其是非艾滋病非传染性疾病的INR。生长因子-15（GDF-15）是一种转化生长因子-β（TGF-β）家族成员，已知可调节细胞衰老和应激反应中涉及的几种生物学过程。由于PLWH表现出过早衰老和代谢失调，我们在ART控制的PLWH(包括INRs和IRs)和健康受试者(HS)中通过ELISA和代谢蛋白测定了GDF-15的血浆水平,并将结果与临床参数相关联.我们发现，与HS相比，PLWH中的GDF-15水平显着升高。GDF-15水平与年龄呈正相关，与体重和LDL胆固醇水平呈负相关。此外，升高的GDF-15水平与PLWH中多种代谢蛋白的差异失调相关。这些结果表明，GDF-15蛋白可能作为代谢失调和衰老的生物标志物。这种生物标志物将在针对ART治疗的PLWH的衰老和代谢紊乱的临床试验中有用。
