Identification of distinct cytokine/chemokine profiles in dermatomyositis with anti-transcriptional intermediary factor 1-γ antibody

Zhao, Qi; Chen, Yongheng; Diao, Licheng; Zhang, Shimin; Wu, Dan; Xue, Feng; Xia, Qing; Li, Hao; Zheng, Jie; Cao, Hua

doi:10.1093/rheumatology/keab625

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…Notarnicola et al ( 31 ) observed increased serum levels of CCL2 in patients with idiopathic inflammatory myopathies, including ASS with anti-Jo-1 antibody. It has been proposed that serum CCL2 might be a good marker for disease activity in DM ( 16 , 29 , 32 – 35 ). Serum CCL2 was closely correlated with TNFR2 in DM and TIMP-1 in ASS.…”

Section: Discussionmentioning

confidence: 99%

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome

et al. 2022

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ObjectivesDermatomyositis (DM) and anti-synthetase syndrome (ASS) are autoimmune diseases with multisystem involvement. Despite sharing some clinical and myopathological features, these are two diseases with different pathogeneses and prognoses. We aimed to clarify and compare cytokine/chemokine profiles in both disorders, which may help in the differential diagnosis.Materials and methodsWe collected clinical data and serum samples of consecutive patients with DM and ASS. Quantibody® Human Inflammation Array 3 for cytokines/chemokines was performed in the serum of all participants. Receiver operating characteristic analysis with the area under the curve and Youden's index were performed.ResultsEight newly diagnosed and treatment-naïve patients with DM, nine newly diagnosed and treatment-naïve patients with ASS, and 14 healthy controls were enrolled. Serum C-C motif chemokine ligand (CCL) 2, CCL4, C-X-C motif chemokine ligand (CXCL) 13, and tumor necrosis factor receptor 2 (TNFR2) were increased in patients with both DM and ASS. Serum interleukin (IL)-1 receptor type 1 (IL-1ra), IL-1b, CCL1, CXCL11, and CCL3 were modulated in patients with DM only, and IL-8, CXCL9, and tissue inhibitors of metalloproteinases-1 (TIMP-1) in patients with ASS only. Serum CCL2, CXCL13, and TNFR2 accurately distinguished patients with DM and ASS from healthy controls, as shown by the area under the curve >0.80. Moreover, receiver operating characteristic analysis showed that, as biomarkers for discrimination between DM and ASS, the combination of IL-1ra and TIMP-1, had an area under the curve of 0.944, a sensitivity of 87.5%, and a specificity of 88.9%.ConclusionOur study demonstrated that serum levels of cytokines/chemokines showed a different pattern in newly diagnosed patients with DM and ASS, in which serum IL-1ra and TIMP-1 could be used to distinguish between the two diseases.

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Section: Discussionmentioning

confidence: 99%

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome

et al. 2022

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“…It is suggested that TNF-α could participate in the pathogenic DM process [34]. Elevated TNF-α serum levels have been shown in anti-TIF1-γ antibody-positive DM patients suffering from significant muscle weakness and elevated cancer rate [35]. Our results were consistent with this finding which further revealed that plasma TNF-α levels in the Cancer TIF1-γ-DM group were significantly higher than in the Non-cancer TIF1γ-DM and HC groups (Figures 2 and 3).…”

Section: Discussionmentioning

confidence: 99%

“…DM is predominantly mediated through humoral immunity involving B cells, CD4 + T cells, macrophages, muscle infiltration, antibodies, and complement-mediated injury of capillaries accompanied by inflammatory cytokine dysregulations [9,10]. Positive correlations between disease severity and serum cytokine levels, including C-X-C motif chemokine ligand 10 (CXCL10), C-C motif chemokine ligand 2 (CCL2), Galectin-9, interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and TNF receptor 1 (TNFR1) were observed within anti-TIF1-γ antibody-positive DM patients [11]. Autoimmune diseases and cancer have a robust inflammatory background mediated by inflammatory cytokines despite displaying fundamentally different pathological conditions [12].…”

Section: Introductionmentioning

confidence: 99%

Circulating VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis

Huang

Liu

et al. 2022

Clin Rheumatol

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Objectives The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients. Methods Twenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database. Results VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients. Conclusion The present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points• VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Graphical abstract

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Serum level of galectin-9 as a potential biomarker for high risk of malignancy in dermatomyositis

Chen

Huang

et al. 2023

Rheumatology

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Objectives Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). Methods Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut-off value of galectin-9. Results Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85-32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42–7.89) ng/ml, P < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (r s = 0.3065, P = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85–38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23–27.91) ng/ml, P = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97–28.02) ng/ml, P = 0.0258], and tumour patients without DM [7.46 (4.90–8.51) ng/ml, P < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04–41.43) ng/ml vs. 13.88 (5.15–20.37) ng/ml, P = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803–0.977) showed the highest predictive value for the presence of cancer in DM. Conclusion Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome.

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Identification of distinct cytokine/chemokine profiles in dermatomyositis with anti-transcriptional intermediary factor 1-γ antibody

Cited by 5 publications

References 38 publications

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome

Circulating VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis

Serum level of galectin-9 as a potential biomarker for high risk of malignancy in dermatomyositis

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