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Abstract Background An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear. Methods A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses. Results Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p < 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p < 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%, p = 0.003; integrated discrimination improvement 5.78%, p = 0.0003). Conclusions sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.

Abstract Background Previous studies showed that soluble IL-2Rα is an important marker of cellular immune activation and might be a marker of treatment efficacy for children with brucellosis. However, data regarding adult patients with brucellosis were unknown. The aim of study was to explore the potential role of serum sIL-2Rα evaluating treatment responses in adult patients with brucellosis, and T cell immune status was also examined. Methods During January 2016–April 2017, 30 patients with acute brucellosis from the Third People’s Hospital of Linfen in Shanxi Province and Beijing Di Tan Hospital, and 28 healthy controls were included in this study. Peripheral blood samples were collected before and after six weeks of antibiotic treatment. Serum sIL-2Rα levels were measured by enzyme-linked immunosorbent assay, and the percentage of Th1, Th2, Tc1, Tc2, and Tregs was detected by flow cytometry after intracellular staining for cytokines (interferon-γ and interleukin-4) and Foxp3 in T lymphocytes from peripheral blood. The obtained data were analyzed with Wilcoxon ranked sum tests for paired values, Mann-Whitney U-tests for comparisons between patients and healthy controls, and Spearman rank tests for correlation analyses. Results Serum sIL-2Rα levels were significantly higher in patients than in controls (P = 0.001). A significant decline was observed in patients after the cessation of treatment (P 0.05). Th1, Tc1, Th2, and Tc2 cell frequencies were higher in patients than in healthy subjects (P

BackgroundA better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.ObjectiveWe aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.Methods139 hospitalized patients with COVID-19−58 mild/moderate and 81 severe/critical—and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8–12 weeks after discharge.ResultsA National Early Warning Score 2 >2 (OR:41.4; CI:10.38–167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88–69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08–12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48–7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4–7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1–5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases.ConclusionA characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a “low T1 lymphocyte signature” was found in severe/critical COVID-19 patients.

Background: Previous studies showed that soluble IL-2Rα is an important marker of cellular immune activation and might be a marker of treatment efficacy for children with brucellosis. However, data regarding adult patients with brucellosis were unknown. The aim of study was to explore the potential role of serum sIL-2Rα evaluating treatment responses in adult patients with brucellosis, and T cell immune status was also examined. Methods: During January 2016–April 2017, 30 patients with acute brucellosis from the Third People's Hospital of Linfen in Shanxi Province and Beijing Di Tan Hospital, and 28 healthy controls were included in this study. Peripheral blood samples were collected before and after six weeks of antibiotic treatment. Serum sIL-2Rα levels were measured by enzyme-linked immunosorbent assay, and the percentage of Th1, Th2, Tc1, Tc2, and Tregs was detected by flow cytometry after intracellular staining for cytokines (interferon-γ and interleukin-4) and Foxp3 in T lymphocytes from peripheral blood. The obtained data were analyzed with Wilcoxon ranked sum tests for paired values, Mann-Whitney U-tests for comparisons between patients and healthy controls, and Spearman rank tests for correlation analyses. Results: Serum sIL-2Rα levels were significantly higher in patients than in controls (P = 0.001). A significant decline was observed in patients after the cessation of treatment (P < 0.001) and return to normal (P > 0.05). Th1, Tc1, Th2, and Tc2 cell frequencies were higher in patients than in healthy subjects (P < 0.05), while the Th1/Th2 and Tc1/Tc2 ratios were significantly lower (P = 0.0305 and 0.0005, respectively) and returned to normal levels after treatment. In patients with acute brucellosis, serum sIL-2Rα levels were negatively correlated with the Th1/Th2 ratio (r = − 0.478, P = 0.028), Tc1/Tc2 ratio (r = − 0.677, P = 0.001), and Tc1 percentage (r = − 0.516, P = 0.017). Serum sIL-2Rα and Tc2 percentages were positively correlated (r = 0.442, P = 0.045). Conclusions: Based on the correlations with Th1/Th2 and Tc1/Tc2 ratios, serum sIL-2Rα levels may reflect the immune response status. sIL-2Rα may be a marker for therapeutic efficacy in acute brucellosis. [ABSTRACT FROM AUTHOR]

Background: To investigate whether sTREM-1, sIL-2Rα, sCD163, and IL-6 predict septic complications following polytrauma. Prospective observational study in a university hospital intensive care unit. Methods: Blood samples were drawn on admission, 24 and 48 h after the injury from 64 adult polytrauma patients. The occurence of infectious complications was investigated. The sepsis-free rates for the multiple trauma patients were considered as end points in the Kaplan-Meier plot analysis. Results: Upon admission, sIL-2Rα mean values were higher in the T group compared to the T&S patients (1789 ± 1027 pg/mL versus 1280 ± 605 pg/mL, p = 0.02). The initial mean values of sTREM-1, IL-6, and sCD163 did not discriminate between the T and T&S groups patients ( p > 0.05). sTREM-1 cutoff was 62 pg/mL: the sepsis-free rates differed significantly between the patients with sTREM-1 concentrations lower and higher than the cutoff (80 versus 48 %, p < 0.01). From the patients with serum sIL-2Rα ≥1593 pg/mL, 86 % did not present sepsis; for sIL-2Rα values in the range 946-1593 pg/mL, the sepsis-free rate was 68 %, while from the patients with sIL-2Rα <945 pg/mL, only 40 % remained sepsis-free (p = 0.05). sCD163 cutoff of 1000 ng/mL did not discriminate between the patients (76 versus 64 %, p = 0.28). For IL-6, the sepsis-free rates differed significantly between the patients with concentrations lower and higher than 400 pg/mL (78 versus 38 %, p < 0.01). Conclusions: sTREM-1, sIL-2Rα, and IL-6, but not CD163, may be used as prognostic markers for the occurrence of sepsis in multiple trauma patients. Level of evidence: Level II-Diagnostic tests and criteria [ABSTRACT FROM AUTHOR]

Introduction: Basal cell carcinoma (BCC) is an immunogenic neoplasm and the imbalance in Th1/Th2 cytokines expression seems to play the major role in pathogenesis and clinical behaviour of the tumour. Aim: To investigate the association of soluble interleukin 2α receptor (sIL-2Rα) and interleukin-2 (IL-2) serum concentrations with BCC. Material and methods: The study involved 110 individuals with BCC and 60 healthy age- and sex-matched volunteers. Serum levels of sIL-2Rα and IL-2 were measured using ELISA test. Results: We found significantly (p = 0.027) increased sIL-2Rα serum levels in BCC patients, in comparison to healthy controls. Statistically (p = 0.04) higher sIL-2Rα levels were observed in patients with more advanced tumours. Serum levels of sIL-2Rα showed a significant linear (r = 0.24, p = 0.018) correlation with tumour size. The average IL-2 serum levels in BCC patients were statistically (p = 0.039) decreased compared to controls. Significantly (p = 0.0454) lower median IL-2 levels were observed in patients with more advanced tumours. A negative correlation between sIL-2Rα and IL-2 serum concentrations was revealed (r = -0.22; p = 0.027). Conclusions: Our results testify to the importance of the IL-2/sIL-2Rα signalling pathway in pathogenesis of BCC, suggesting that IL-2 and sIL-2Rα might be considered as potential markers of disease and targets for immunotherapy in BCC patients. [ABSTRACT FROM AUTHOR]

We identified and validated several novel inflammatory markers of cognitive performance in community-living older persons. An exploratory study (n = 83) correlated 177 inflammatory markers assayed by Luminex with the Mini–Mental State Examination (MMSE) and identified 8 inflammatory markers for enzyme-linked immunosorbent assay (ELISA) and correlations with MMSE, Montreal Cognitive Assessment (MoCA), and cognitive impairment in the validation study (n = 139). The validation study replicated the significant associations of soluble interleukin-2 receptor alpha chain (sIL-2Rα; p = 0.050), soluble tumor necrosis factor receptor 2 (sTNFR2; p = 0.002) and soluble glycoprotein 130 (sgp130; p = 0.026) with MMSE, and sIL-2Rα ( p = 0.019) and sgp130 ( p < 0.001) with MoCA. Significant trends of associations of tertiles of sgp130, sIL-2Rα, and sTNFR2 were found with cognitive impairment. Highly elevated estimates of association of high versus low tertiles were obtained for sgp130 (odds ratio [OR] = 4.24, 95% confidence interval [CI] 0.96–18.8), sIL-2Rα (OR = 3.94, 95% CI 0.83–18.7), and sTNFR2 (OR = 7.58, 95% CI 1.19–48.1). sgp130, sTNFR2, and sIL-2Rα are promising inflammatory markers of low cognitive performance for further investigation. [ABSTRACT FROM AUTHOR]

Background: T-cell malignancies are heterogeneous in their clinical presentation and pathology, and have a poor prognosis. New biomarkers are needed to predict prognosis and to provide insights into signal pathways used by these cells. The goal of this study was to evaluate pretreatment serum cytokines in patients with newly diagnosed T-cell neoplasms and correlate with clinical outcome. Patients and methods: We evaluated 30 cytokines in pretreatment serum from 68 untreated patients and 14 normal controls. Significantly elevated cytokines were correlated with patterns of abnormalities, event-free survival (EFS) and overall survival (OS). Results: Our data demonstrated significantly elevated levels (versus controls) of seven cytokines--epidermal growth factor (EGF), IL-6, IL-12, interferon gamma-induced protein (IP)-10, soluble interleukin (sIL)-2Rα, monokine induced by gamma interferon (MIG), and IL-1 RA--in all T-cell neoplasms (P<0.05). In the angioimmunoblastic subset, all seven cytokines except IP-10 and in the peripheral T-cell lymphoma (TCL)-not otherwise specified subset, only IP-10, sIL-2Rα, MIG, and IL-8 were statistically elevated compared with control. Of these, elevated cytokines all but EGF were predictive of an inferior EFS; IL-1RA, sIL-2Rα, and MIG predicted an inferior OS. In a multivariate analysis, sIL-2Rα [hazard ratio (HR) = 3.95; 95% confidence interval (CI) 1.61 -8.38] and IL-1 RA (HR = 3.28; 95% CI 1.47-7.29) levels remained independent predictors of inferior EFS. TCL cell lines secreted high levels of sIL-2Rα and expressed the IL-2Rα surface receptor. Conclusions: This report describes the cytokines relevant to prognosis in patients with untreated TCL and provides the rationale to include serum IL-1 RA and sIL-2Rα as biomarkers in future trials. Inhibition of these cytokines may also be of therapeutic benefit. [ABSTRACT FROM AUTHOR]

Background: A better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options., Objective: We aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19., Methods: 139 hospitalized patients with COVID-19-58 mild/moderate and 81 severe/critical-and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8-12 weeks after discharge., Results: A National Early Warning Score 2 >2 (OR:41.4; CI:10.38-167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88-69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08-12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48-7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4-7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1-5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases., Conclusion: A characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a "low T1 lymphocyte signature" was found in severe/critical COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcia-Gasalla, Berman-Riu, Pons, Rodríguez, Iglesias, Martínez-Pomar, Llompart-Alabern, Riera, Ferré Beltrán, Figueras-Castilla, Murillas and Ferrer.)

• Biomarkers of systemic inflammation (TNFα and CRP) correlate with sIL-2Rα in healthy subjects. • In MS patients, sIL-2Rα does not correlate with biomarkers of systemic inflammation. • No association between biomarkers of systemic inflammation and the IL2RA SNP rs2104286. Soluble interleukin-2 (IL-2) receptor α (sIL-2Rα) antagonizes IL-2 signaling and is involved in the pathogenesis of several immune-mediated diseases including multiple sclerosis (MS). The level of sIL-2Rα is affected by the MS-associated single nucleotide polymorphism (SNP) rs2104286. By use of ELISA and electrochemiluminescence, we investigated if 26 biomarkers of systemic inflammation were associated with sIL-2Rα and rs2104286 in cohorts of healthy subjects and MS patients in serum and heparin plasma. We found that sIL-2Rα significantly correlated with the level of tumor necrosis factor-α (TNFα) (r = 0.391, p = 0.002) in healthy subjects and the association was validated in a separate cohort. Additional, in healthy subjects we confirmed a previous report indicating that C-reactive protein (CRP) correlates with sIL-2Rα (r = 0.278, p = 0.034). None of the biomarkers of systemic inflammation were significantly associated with sIL-2Rα in MS patients. Furthermore, the MS-associated SNP rs2104286 was not significantly associated with any of the biomarkers of systemic inflammation in neither healthy subjects nor MS patients. We conclude that sIL-2Rα is associated with TNFα and CRP in healthy subjects. However, further research is required to confirm the use of sIL-2Rα as biomarker of systemic inflammation as well as to assess the mechanism underlying the observed correlation between levels of sIL-2Rα and TNFα. [ABSTRACT FROM AUTHOR]

• Cancer microenvironment modulates sensitivity to therapy. • Serum levels of cytokines and soluble adhesion molecules correlate in AML. • Serum soluble receptors for inerleukin-2 and TNF-α are prognostic indicators in AML. Acute myeloid leukemia (AML) cells are highly resistant to chemotherapeutic drugs. Cytokines and adhesion molecules may contribute to this resistance and affect treatment outcome. The aim of this study was to evaluate the independence and additional prognostic information of baseline serum levels of selected cytokines and soluble adhesion molecules, included in analyses with standard prognostic indicators. We used biochip array technology to measure levels of selected cytokines and soluble adhesion molecules in serum samples of 80 newly diagnosed AML patients. The markers of tumour microenvironment were analysed against high risk karyotype, hyperleucocytosis, higher age, lactic dehydrogenase levels and presence of FLT3-ITD and NPM-1 mutation. All evaluated analytes were independent of standard prognostic indicators. Fifteen were associated with overall and eight with progression-free survival in univariate analysis. After correction for multiple testing, we identified soluble interleukin-2 receptor-α as an independent indicator of overall survival. Further, the soluble type I TNF-α receptor was close to statistical significance for both overall and progression-free survival. Baseline levels of soluble interleukin-2 receptor-α predict overall survival in newly diagnosed AML. The TNF-α type I soluble receptor is a candidate prognostic marker in AML and is worth of further investigation. [ABSTRACT FROM AUTHOR]

Biochemical processes have been associated with the pathogenesis of mild cognitive impairment (MCI) and dementia, including chronic inflammation, dysregulation of membrane lipids and disruption of neurotransmitter pathways. However, research investigating biomarkers of these processes in MCI remained sparse and inconsistent. To collect fresh evidence, we evaluated the performance of several potential markers in a cohort of 57 MCI patients and 57 cognitively healthy controls. MCI patients showed obviously increased levels of plasma TNF-α (p = 0.045) and C-peptide (p = 0.004) as well as decreased levels of VEGF-A (p = 0.042) and PAI-1 (p = 0.019), compared with controls. In addition, our study detected significant correlations of plasma sTNFR-1 (MCI + Control: B = -6.529, p = 0.020; MCI: B = -9.865, p = 0.011) and sIL-2Rα (MCI + Control: B = -7.010, p = 0.007; MCI: B = -11.834, p = 0.003) levels with MoCA scores in the whole cohort and the MCI group. These findings corroborate the inflammatory and vascular hypothesis for dementia. Future studies are warranted to determine their potential as early biomarkers for cognitive deficits and explore the related mechanisms.