A comprehensive profile of chemokines in the peripheral blood and vascular tissue of patients with Takayasu arteritis

Kong, Xiaoni; Wu, Shuang; Dai, Xiaojuan; Yu, Wandong; Wang, Jinghua; Sun, Ying; Ma, Li; Dai, X.; Chen, Huiyong

doi:10.1186/s13075-022-02740-x

Cited by 11 publications

(16 citation statements)

References 49 publications

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“…Another study evaluated serum chemokines such as CXCL10, CXCL13, CCL5, and CXCL8 in TAK patients, but none showed signi cant differences between active disease and remission 29 . In line with these ndings, Kong et al also found no differences in the levels of CCL5, CXCL16, CXCL11, and IL-16 between patients with active disease and those in remission 30 .…”

Section: Discussionmentioning

confidence: 69%

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Monocyte subsets and monocyte-related chemokines in Takayasu arteritis

Aguiar

Torquato

Salu

et al. 2022

Preprint

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Background: The pathogenesis of Takayasu arteritis (TAK) is poorly understood. Although a macrophage-rich vessel wall granulomatous inflammation is a hallmark of TAK pathology, no previous studies have analyzed the monocytes’ role in the pathogenesis of the disease. This study aims to evaluate the distribution of monocyte subsets and the monocyte-related chemokines profile in the peripheral blood of TAK patients and age & sex matched healthy controls (HC). Methods: TAK patients were evaluated for current disease activity and current therapy. Monocyte subsets were identified by flow cytometry according to the surface expression of CD14 and CD16 as classical (CD14+CD16-), intermediate (CD14+CD16dim), and non-classical (CD14dimCD16high) in the peripheral blood. Multiplex Luminex assay was used to measure serum monocytes-related chemokines including CCL2, CCL3, CCL4, CCL5, CCL7, CXCL10 and CX3CL1. Results: Thirty-two consecutive TA patients and 30 HC were evaluated. TAK patients had a higher number of circulating intermediate monocytes compared to HC [25.01 cells x 106/L (16.7-52.0) vs. 17.2 cells x 106/L (9.2-25.3); p = 0.014]. Active disease was associated with monocytosis (p = 0.004) along with the increase of the classical (p = 0.003) and intermediate (p < 0.001) subsets compared to HC. No significant differences were found in the distribution of monocyte subsets between active disease and the remission state. Prednisone use reduced the percentage of non-classical monocytes (p = 0.011). TAK patients had lower CCL3 (p = 0.033) and CCL4 (p = 0.023) levels than HC, whereas CCL22 levels were higher in active TAK compared to the remission state (p = 0.008). Therapy with immunosuppressive agents or biologics did not impact serum chemokines, but glucocorticoids were associated with lower CXCL10 levels (p = 0.012). In TAK patients, CCL4 concentration correlated with the number of total monocytes (Rho = 0.489; p = 0.005) and classical and intermediate monocytes (Rho = 0.448; p = 0.010 and Rho = 0.412; p = 0.019) in the peripheral blood. Conclusions: TAK is associated with altered counts of monocyte subsets in the peripheral blood compared to HC and CCL22 is the chemokine with the strongest association with active disease in TAK.

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Section: Discussionmentioning

confidence: 69%

“…Persistently high serum CCL22 levels have been described in TAK patients compared to HC 30 , and a further increase in its levels was observed even after therapy for TAK. Our study, however, was the rst to describe signi cant differences between active disease and remission regarding CCL22 serum levels in TAK.…”

Section: Discussionmentioning

confidence: 98%

Monocyte subsets and monocyte-related chemokines in Takayasu arteritis

Aguiar

Torquato

Salu

et al. 2022

Preprint

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“…Pathway enrichment analyses, both Reactome and KEGG pathway, revealed that cytokines and chemokines are playing a critical role in the pathogenesis of TA. Evaluated chemokines in Frontiers in Genetics frontiersin.org vessel tissues of TA with immunofluorescence and immunohistochemistry staining and identified CCL22, RANTES, CXCL16, CXCL11, and IL-16 as the major chemokines recruiting immune cells in the vascular tissue of patients with TA (Kong et al, 2022). As to cytokines and its receptor, found out increased expression of IL-1R2 genes in PBMCs of patients with TA.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis

Miao

Gao

et al. 2022

Front. Genet.

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Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently (p < 0.05 and Log2FC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.

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“…Further validating these chemokines in 20 TAK patients and 20 healthy controls, five chemokines (CCL22, RANTES, CXCL11, CXCL16, IL-16) were confirmed to be elevated in TAK. However, none of these cytokines were associated with ESR or CRP or were significantly different between active and inactive TAK in a separate cohort of 25 patients with TAK [ 146 ].…”

Section: Circulating Biomarkers Of Disease Activity In Takmentioning

confidence: 99%

Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis

et al. 2022

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Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.

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A comprehensive profile of chemokines in the peripheral blood and vascular tissue of patients with Takayasu arteritis

Cited by 11 publications

References 49 publications

Monocyte subsets and monocyte-related chemokines in Takayasu arteritis

Monocyte subsets and monocyte-related chemokines in Takayasu arteritis

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis

Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis

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