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Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis.

ABSTRACT: Objective: To investigate the relationship of interleukin (IL)-35 with sarcoidosis. Methods: We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of p35, EBI3, and GAPDH in CD19⁺ cells and CD4⁺ cells were detected by real-time PCR. Sarcoidosis granuloma mice models were established with Propionibacterium acnes (PA) and one group was treated with IL-35 antibodies. Proportions of Breg, Tfh, and Treg cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) were detected by FCM. Results: The IL-35 levels and the proportions of Breg and Tfh cells in the peripheral blood of patients with active sarcoidosis were significantly higher compared to patients with stable sarcoidosis and healthy controls. Moreover, the IL-35 level in patients with progressive disease was lower than that found at the initial visit. EBI3 and p35 mRNA levels in CD19⁺ cells for patients with active sarcoidosis were significantly higher as compared to patients with stable sarcoidosis and healthy controls, while there were no significant differences in p35 and EBI3 mRNA levels in CD4⁺ cells between the three groups. In the mouse model of sarcoidosis, there were loose granulomata (macrophage accumulation in the bronchial areas and immature granuloma) after intervention with IL-35 antibodies. Meanwhile, the proportions of Breg cells in the peripheral blood and BALF of the model were significantly increased, while the proportion of Treg cells declined significantly. After intervention with IL-35 antibodies, the proportion of Breg cells in the peripheral blood of mice decreased significantly as compared to the mice not exposed to anti-IL-35 antibodies. Conclusion: IL-35 levels increased significantly in the serum of patients with active sarcoidosis, and lower IL-35 levels were correlated with persistent disease. Serum IL-35 levels might be better correlated with Breg cell functions.

SUBMITTER: Mengmeng Z

PROVIDER: S-EPMC7248598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis.

Mengmeng Zhao Z Jiacui Song S Shanshan Du D Yuan Zhang Z Ying Zhou Z Qiuhong Li L Dong Weng W Hui-Ping Li L

Frontiers in immunology 20200519

<b>Objective:</b> To investigate the relationship of interleukin (IL)-35 with sarcoidosis. <b>Methods:</b> We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of ...[more]

PMID: 32508842

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Project description:BACKGROUND: Both type I interferon (IFN), also known as IFN-? and tumor necrosis factor alpha (TNF-?) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes. METHODS: We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-? was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations. RESULTS: Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-? levels were significantly higher relative to matched controls (P?=?0.039), and patients with neurologic disease had significantly higher TNF-? than patients lacking this manifestation (P?=?0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P?=?0.0032). None of the associations observed were shared between the two ancestral groups. CONCLUSIONS: Our data indicate that significant associations between serum levels of TNF-? and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.

Project description:ObjectiveExisting evidence suggests that chronic inflammation promotes the progression of human intracranial aneurysm (IA) and many cytokines have been detected to participate in the process of inflammation. However, rare cytokines in plasma have been used as proxies for progression of IA. This study aimed to identify novel cytokines as biomarkers to predict the development of IA.MethodsPatients with unruptured intracranial aneurysms (UIAs) undergoing microsurgical clipping were prospectively recruited from January 2017 to June 2020 and were separated into two groups based on their ELAPSS score (low risk group < 10, intermediate-high risk group ≥ 10). Propensity score matching (PSM) was used to reduce imbalances in the baseline characteristics between groups. All blood samples were collected before surgery. A human serum 48-cytokines examination was performed to analyze the concentrations of serological cytokines. Clinical data and cytokines were compared between groups.ResultsA total of 184 patients were enrolled in this study. The low risk group contained 77 patients and 107 patients were included in the intermediate-high risk group. Finally, there were 69 patients in each group after PSM with a matching rate of 1:1. The concentrations of 3 serum cytokines were significantly increased in intermediate-high risk patients, namely, interleukin-15 (IL-15), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-β (TNF-β) (P < 0.05, |log2 fold change| > 2). The result of receiver operator characteristic (ROC)curve revealed that TNF-β had the highest predictive accuracy, with an area under the curve (AUC) value of 0.725 [95% confidence interval (CI) 0.639-0.811, P < 0.001] followed by IL-15 (AUC = 0.691, 95% CI 0.602-0.781, P < 0.001) and MCP-1 (AUC = 0.661, 95% CI 0.569-0.753, P = 0.001). Multivariate logistic analysis demonstrated high IL-15 [odds ratio (OR), 3.23; 95% CI, 1.47-7.12; P = 0.004] and high TNF-β (OR, 8.30; 95% CI, 3.25-21.25; P < 0.001) as the risk factors that correlated with intermediate-high risk of IA progression.ConclusionUIA patients with intermediate-high growth risk exhibited increased serum levels of IL-15, MCP-1, and TNF-β. Serum IL-15, and TNF-β could serve as biomarkers to predict the progression of UIAs.

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Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis.

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Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis.

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