Multimarker profiling identifies protective and harmful immune processes in heart failure: findings from BIOSTAT-CHF.
Multimarker profiling identifies protective and harmful immune processes in heart failure: findings from BIOSTAT-CHF.
复制标题
DOI：
10.1093/cvr/cvab235
复制
发表时间：
2022-06-29
影响因子：
10.8
通讯作者：
中科院分区：
文献类型：
--
作者：
探索新的免疫调节干预措施，以改善心力衰竭（HF）的结果受到阻碍的复杂性/冗余的炎症途径，这仍然是知之甚少。因此，我们的目的是研究HF患者不同免疫过程的激活与结局之间的相关性。我们测量了2022例HF恶化患者和一个独立验证队列（n = 1691）（BIOSTAT-CHF指数和验证队列）中的355种生物标志物，并根据其功能将其分类为基于基因本体分类的生物过程。主成分分析用于提取每个过程的加权评分。我们研究了这些过程与2年随访时全因死亡率的相关性。使用每种生物标志物对过程的加权评分的贡献来鉴定潜在的治疗靶点。平均年龄为69（±12.0）岁，537例（27%）患者为女性。我们确定了64个独特的、代表性过高的免疫相关过程，代表了355个生物标志物中的188个。在这些过程中，19个与全因死亡率相关（10个阳性，9个阴性）。在外部验证后，“T细胞共刺激”和“对干扰素-γ的反应/干扰素-γ产生的正调节”的激活增加分别与全因死亡率呈最一致的正相关和负相关。在T细胞共刺激，诱导共刺激配体，CD 28，CD 70和肿瘤坏死因子超家族成员-14被确定为潜在的治疗靶点。我们证明了不同的免疫过程在HF中的不同保护和有害作用，并提出了新的治疗靶点。这些发现构成了一个丰富的知识基础，为未来的HF炎症研究提供信息。
The exploration of novel immunomodulatory interventions to improve outcome in heart failure (HF) is hampered by the complexity/redundancies of inflammatory pathways, which remain poorly understood. We thus aimed to investigate the associations between the activation of diverse immune processes and outcomes in patients with HF. We measured 355 biomarkers in 2022 patients with worsening HF and an independent validation cohort (n = 1691) (BIOSTAT-CHF index and validation cohorts), and classified them according to their functions into biological processes based on the gene ontology classification. Principal component analyses were used to extract weighted scores per process. We investigated the association of these processes with all-cause mortality at 2-year follow-up. The contribution of each biomarker to the weighted score(s) of the processes was used to identify potential therapeutic targets. Mean age was 69 (±12.0) years and 537 (27%) patients were women. We identified 64 unique overrepresented immune-related processes representing 188 of 355 biomarkers. Of these processes, 19 were associated with all-cause mortality (10 positively and 9 negatively). Increased activation of ‘T-cell costimulation’ and ‘response to interferon-gamma/positive regulation of interferon-gamma production’ showed the most consistent positive and negative associations with all-cause mortality, respectively, after external validation. Within T-cell costimulation, inducible costimulator ligand, CD28, CD70, and tumour necrosis factor superfamily member-14 were identified as potential therapeutic targets. We demonstrate the divergent protective and harmful effects of different immune processes in HF and suggest novel therapeutic targets. These findings constitute a rich knowledge base for informing future studies of inflammation in HF.
登录
查看更多内容
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
4.4
作者：
Barin, Jobert G.;Baldeviano, G. Christian;Cihakova, Daniela
通讯作者：
Cihakova, Daniela
影响因子：
5.4
作者：
Klingenberg, R;Autschbach, F;Dengler, TJ
通讯作者：
Dengler, TJ
DOI：
10.1073/pnas.0408241102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Afanasyeva, M;Georgakopoulos, D;Rose, NR
通讯作者：
Rose, NR