High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

Ge, Peicong; Liu, Chenglong; Chan, Liujia; Pang, Yuheng; Li, Hao; Zhang, Qian; Ye, Xun; Wang, Jia; Wang, Rong; Zhang, Yan; Wang, Wenjing; Zhang, Dong; Zhao, Jizong

doi:10.3389/fimmu.2022.922000

Cited by 14 publications

(9 citation statements)

References 44 publications

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“…Inflammatory processes play a significant role in the development of IA 30,31 . Several research exploring the association between chronic inflammation and IAs suggested that persistent disruption of the peripheral immune environment may induce the formation of IAs through inflammatory cascades 32–35 . In the present, it was observed that PBMCs, as a crucial component of the peripheral immune environment, exhibited metabolic dysregulation associated with numerous diseases.…”

Section: Discussionmentioning

confidence: 51%

“…30,31 Several research exploring the association between chronic inflammation and IAs suggested that persistent disruption of the peripheral immune environment may induce the formation of IAs through inflammatory cascades. [32][33][34][35] In the present, it was observed that PBMCs, as a crucial component of the peripheral immune environment, exhibited metabolic dysregulation associated with numerous diseases. In our study, metabolic profiling of PBMCs revealed distinct metabolic characteristics among different subsets.…”

Section: Discussionmentioning

confidence: 72%

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Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients

Ya,

Ma,

Liu

et al. 2024

Clinical & Translational Med

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BackgroundIntracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain.MethodsSingle‐cell Cytometry by Time‐of‐Flight (CyTOF) technology was employed to profile the single‐cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression.ResultsDifferent subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up‐regulated in T cells, B cells and monocytes from the controls but down‐regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti‐inflammatory functional molecules (IL‐4 and IL‐10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out‐of‐bag errors).ConclusionThese findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 72%

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients

Ya,

Ma,

Liu

et al. 2024

Clinical & Translational Med

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“…It is increasingly recognized that intracranial aneurysm is a disease that is driven by chronic inflammation (2,4,7). The SII index is a peripheral blood inflammatory index that is used to evaluate systemic inflammation (10), whereas AWE is regarded as a biomarker of aneurysmal wall inflammation (5).…”

Section: Discussionmentioning

confidence: 99%

“…In a pathological study, it was reported that the status of inflammatory processes in the aneurysmal wall correlates well with aneurysmal wall enhancement (AWE) in highresolution magnetic resonance imaging (HR-MRI) (5). Inflammatory processes in the aneurysmal wall also involve the local activation of the immune system, including neutrophil influx followed by the infiltration of macrophages and other inflammatory cells (6,7). It has been reported that cytokine interleukin-10 and the neutrophil to lymphocyte ratio (NLR) are associated with AWE in HR-MRI (8,9).…”

Section: Introductionmentioning

confidence: 99%

Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms

Peng

Xia²,

Niu³

et al. 2023

Front. Immunol.

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IntroductionInflammation plays a key role in the progression of intracranial aneurysms. Aneurysmal wall enhancement (AWE) correlates well with inflammatory processes in the aneurysmal wall. Understanding the potential associations between blood inflammatory indices and AWE may aid in the further understanding of intracranial aneurysm pathophysiology.MethodsWe retrospectively reviewed 122 patients with intracranial fusiform aneurysms (IFAs) who underwent both high-resolution magnetic resonance imaging and blood laboratory tests. AWE was defined as a contrast ratio of the signal intensity of the aneurysmal wall to that of the pituitary stalk ≥ 0.90. The systemic immune-inflammation (SII) index (neutrophils × platelets/lymphocytes) was calculated from laboratory data and dichotomized based on whether or not the IFA had AWE. Aneurysmal symptoms were defined as sentinel headache or oculomotor nerve palsy. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to determine how well the SII index was able to predict AWE and aneurysmal symptoms. Spearman’s correlation coefficients were used to explore the potential associations between variables.ResultsThis study included 95 patients, of whom 24 (25.3%) presented with AWE. After adjusting for baseline differences in neutrophil to lymphocyte ratios, leukocytes, and neutrophils in the multivariable logistic regression analysis, smoking history (P = 0.002), aneurysmal symptoms (P = 0.047), maximum diameter (P = 0.048), and SII index (P = 0.022) all predicted AWE. The SII index (P = 0.038) was the only independent predictor of aneurysmal symptoms. The receiver operating characteristic curve analysis revealed that the SII index was able to accurately distinguish IFAs with AWE (area under the curve = 0.746) and aneurysmal symptoms (area under the curve = 0.739).DiscussionAn early elevation in the SII index can independently predict AWE in IFAs and is a potential new biomarker for predicting IFA instability.

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“…NK cell activation may play a significant role in the exacerbation of AS (21), suggesting that the increased cytotoxicity mediated by NK cells may contribute to the development of AS. Moreover, the migration ability of NK cells in the peripheral blood of patients with IA is also enhanced (22). NK cells may aggregate and activate in the aneurysm wall during the pathogenesis, which mediates cytotoxicity to promote disease progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of co-expressed central genes and transcription factors in atherosclerosis-related intracranial aneurysm

et al. 2023

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BackgroundNumerous clinical studies have shown that atherosclerosis is one of the risk factors for intracranial aneurysms. Calcifications in the intracranial aneurysm walls are frequently correlated with atherosclerosis. However, the pathogenesis of atherosclerosis-related intracranial aneurysms remains unclear. This study aims to investigate this mechanism.MethodsThe Gene Expression Omnibus (GEO) database was used to download the gene expression profiles for atherosclerosis (GSE100927) and intracranial aneurysms (GSE75436). Following the identification of the common differentially expressed genes (DEGs) of atherosclerosis and intracranial aneurysm, the network creation of protein interactions, functional annotation, the identification of hub genes, and co-expression analysis were conducted. Thereafter, we predicted the transcription factors (TF) of hub genes and verified their expressions.ResultsA total of 270 common (62 downregulated and 208 upregulated) DEGs were identified for subsequent analysis. Functional analyses highlighted the significant role of phagocytosis, cytotoxicity, and T-cell receptor signaling pathways in this disease progression. Eight hub genes were identified and verified, namely, CCR5, FCGR3A, IL10RA, ITGAX, LCP2, PTPRC, TLR2, and TYROBP. Two TFs were also predicted and verified, which were IKZF1 and SPI1.ConclusionIntracranial aneurysms are correlated with atherosclerosis. We identified several hub genes for atherosclerosis-related intracranial aneurysms and explored the underlying pathogenesis. These discoveries may provide new insights for future experiments and clinical practice.

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High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

Cited by 14 publications

References 44 publications

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients

Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms

Identification of co-expressed central genes and transcription factors in atherosclerosis-related intracranial aneurysm

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