Lucy Kundura, Renaud Cezar, Sandrine Gimenez, Manuela Pastore, Christelle Reynes, Albert Sotto, Jacques Reynes, Clotilde Allavena, Laurence Meyer, Alain Makinson, Pierre Corbeau
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Soluble markers of inflammation, and monocyte activation and endothelial activation were measured by ELISA. The participants' immune activation was profiled by an unsupervised double hierarchical clustering analysis. We used ANOVA p-values to rank immunomarkers most related to Fried score. A Linear Discriminant Analysis (LDA) was performed to link immune activation markers to frailty.</p><p><strong>Results: </strong>41% of the participants were pre-frail, including 24% with a Fried score of 1, and 17% with a Fried score of 2. ANOVA identified the 14 markers of T cell, monocyte, NK cell, endothelial activation, and inflammation the most linked to Fried 3 classes. The LDA performed with these 14 markers was capable of discriminating volunteers according to their Fried score. Two out of the 5 immune activation profiles revealed by the hierarchical clustering were linked to and predictive of pre-frailty. 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Further studies will indicate whether this frailty signature is specific or not of HIV infection, and whether it also precedes frailty in the general population.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935995/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study.\",\"authors\":\"Lucy Kundura, Renaud Cezar, Sandrine Gimenez, Manuela Pastore, Christelle Reynes, Albert Sotto, Jacques Reynes, Clotilde Allavena, Laurence Meyer, Alain Makinson, Pierre Corbeau\",\"doi\":\"10.1186/s12979-024-00416-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>People living with HIV (PLWH) are at risk of frailty, which is predictive for death. 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引用次数: 0
摘要
背景:艾滋病病毒感染者(PLWH)有虚弱的风险,而虚弱可预测死亡。免疫系统的过度活跃被认为是造成虚弱的原因,因此我们对与虚弱有关的免疫激活特征进行了描述:我们对 46 名病毒学应答者(4 名女性和 42 名男性;中位年龄 74 岁;中位感染持续时间 24 年;中位检测不到持续时间 13 年)的 27 种活化标记物进行了量化。T细胞和NK细胞的活化通过流式细胞术进行评估,使用的是细胞表面标记物。炎症、单核细胞活化和内皮细胞活化的可溶性标记物则通过酶联免疫吸附试验(ELISA)进行测量。通过无监督双分层聚类分析对参与者的免疫激活情况进行了分析。我们使用方差分析 p 值对与弗里德评分关系最大的免疫标志物进行了排序。我们采用线性判别分析(LDA)将免疫活化标志物与虚弱程度联系起来:方差分析发现,T 细胞、单核细胞、NK 细胞、内皮细胞活化和炎症等 14 个标记物与 Fried 3 级最有关联。利用这 14 个标记物进行的 LDA 能够根据志愿者的弗里德评分对其进行区分。分层聚类所揭示的 5 个免疫活化特征中,有两个与虚弱前期有关,并可预测虚弱前期。这两个特征是 CD4 T 细胞比例低,CD8 T 细胞、活化的 CD4 T 细胞、CD8 T 细胞、NK 细胞和炎症比例高:我们发现了一种与 PLWH 老年前期相关的免疫激活特征。对有可能发展成虚弱的参与者进行分析,可能有助于有针对性地筛查和预防因丧失活力而导致的医疗并发症。进一步的研究将表明这种虚弱特征是否是艾滋病感染的特异性特征,以及它是否也先于普通人群中的虚弱特征。
Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study.
Background: People living with HIV (PLWH) are at risk of frailty, which is predictive for death. As an overactivity of the immune system is thought to fuel frailty, we characterized the immune activation profiles linked to frailty.
Methods: We quantified twenty-seven activation markers in forty-six virological responders (four females and forty-two males; median age, 74 years; median duration of infection, 24 years; median duration of undetectability, 13 years), whose frailty was determined according to the Fried criteria. T cell and NK cell activation was evaluated by flow cytometry, using a panel of cell surface markers. Soluble markers of inflammation, and monocyte activation and endothelial activation were measured by ELISA. The participants' immune activation was profiled by an unsupervised double hierarchical clustering analysis. We used ANOVA p-values to rank immunomarkers most related to Fried score. A Linear Discriminant Analysis (LDA) was performed to link immune activation markers to frailty.
Results: 41% of the participants were pre-frail, including 24% with a Fried score of 1, and 17% with a Fried score of 2. ANOVA identified the 14 markers of T cell, monocyte, NK cell, endothelial activation, and inflammation the most linked to Fried 3 classes. The LDA performed with these 14 markers was capable of discriminating volunteers according to their Fried score. Two out of the 5 immune activation profiles revealed by the hierarchical clustering were linked to and predictive of pre-frailty. These two profiles were characterized by a low percentage of CD4 T cells and a high percentage of CD8 T cells, activated CD4 T cells, CD8 T cells, and NK cells, and inflammation.
Conclusions: We identified a particular immune activation profile associated with pre-frailty in PLWH. Profiling participants at risk of developing frailty might help to tailor the screening and prevention of medical complications fueled by loss of robustness. Further studies will indicate whether this frailty signature is specific or not of HIV infection, and whether it also precedes frailty in the general population.
期刊介绍:
Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.