Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.
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ABSTRACT:
SUBMITTER: Angulo J
PROVIDER: S-EPMC5529019 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor ? gene (TNF-?). METHODS:A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629. RESULTS:Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-? SNP rs1800629 (TNF -308G>A). CONCLUSIONS:The IL28B SNPs rs12979860 and rs8099917, but not TNF-? SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis.
| S-EPMC4657541 | biostudies-literature
Project description:BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles' pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics' efficacy.ObjectivesThis study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD.MethodsWe retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression.ResultsIL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression.ConclusionsSerum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.
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Project description:Interleukin 16 (IL-16) has been described as a significant cytokine involved in the recruitment of CD4+ cells during inflammation; however, its potential role in psoriasis has not been defined. Our aim was to investigate the IL-16 serum levels and IL-16 mRNA skin expression in psoriasis patients in correlation with disease severity and mRNA skin expression for CD4. Moreover, the IL-16 skin localization was assessed and the -295 T/C IL-16 polymorphism was analyzed. For this exploratory, observational, and cross-sectional study, 97 unrelated patients with chronic plaque type psoriasis and 104 healthy controls were enrolled. IL-16 serum levels were significantly increased in patients compared with controls (P = 0.000022) and positively correlated with Psoriasis Area and Severity Index (r = 0.34, P = 0.0007), Body Surface Area (r = 0.34, P = 0.01) and were significantly higher in individuals with moderate to severe psoriasis (P = 0.0029). There was no significant correlation between IL-16 serum levels and Dermatology Quality of Life Index and no differences in genotype and allele frequencies for -295 T/C IL-16 polymorphism. The expression of IL-16 (mRNA and protein) was elevated in the margin of psoriatic skin while statistically significant increase in IL-16 immunoreactivity, but not in mRNA level, was observed within plaques. Furthermore, the IL-16 mRNA levels within psoriatic lesions positively correlated with the levels of CD4 mRNA, but not with Psoriasis Area and Severity Index. In conclusion, our data revealed an association between circulating IL-16 and severity of psoriasis which indicates that this cytokine could serve as a potential marker of disease activity. However, further investigations are required.
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Project description:UnlabelledThe aim of this study was to investigate serum IL17 levels in patients with Crohn's disease (CD) and to investigate the relationship between serum IL17 levels with disease activity.MethodsFifty patients with CD and sex- and age-matched 40 healthy controls were included in the study. The serum IL17 levels, complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured, and Crohn's disease activity was calculated using Crohn's disease activity index (CDAI).ResultsThe mean serum IL17 level of CD patients did not differ from those of healthy controls (P > 0.05). There was no difference between the mean serum IL levels of active CD patients and of quiescent CD patients (P > 0.05). However, the mean IL17 level of active patients was lower than of control subjects (P = 0.02). Serum IL17 was not correlated with inflammatory markers (ESR, CRP, white blood count, platelet count, and albumin) and CDAI.ConclusionsPeripheral blood serum IL17 levels of CD patients were not higher than of healthy controls, and also, serum IL17 level was not correlated with clinical disease activity. Peripheral IL17 measurement is not a useful tool for detecting and monitoring Crohn's disease which is understood to have complex etiopathogenesis.
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Project description:Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p < 0.001). In addition, IL-28A/IFN-λ2 was statistically significantly inversely correlated with the time from disease onset to negative SARS-CoV-2 PCR results (p = 0.049). Multivariable logistic regression analysis showed that IL-28A/IFN-λ2 was an independent predictor of disease severity (p = 0.021). The low expression of IL-28A/IFN-λ2 may serve as a serum biomarker that predicts the severity of COVID-19, possibly through the mechanism of delayed viral elimination.
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Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.
| S-EPMC5479876 | biostudies-other
Project description:BACKGROUND Few studies have investigated systemic inflammation levels in degenerative cervical myelopathy (DCM). This study evaluated the concentration of inflammatory cytokines in DCM patients and assessed whether they can predict symptom severity. MATERIAL AND METHODS A total of 40 consecutive DCM patients and 10 healthy volunteers were included in this study. Concentrations of interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α were compared between DCM patients and normal controls. Spearman's correlation coefficient was used to examine relationships of cytokines with age, body mass index (BMI), symptom duration, and symptom severity. A DCM compression rat model was established to examine the levels of inflammatory cytokines in serum and cerebrospinal fluid (CSF). RESULTS Serum level of IL-6 is significantly higher in DCM patients compared with normal people (0.8±0.5 pg/ml vs. 0.5±0.3 pg/ml, P=0.036). Positive correlations were found between IL-6 levels with BMI (r=0.519; P=0.001) and symptom severity (ρ=-0.556, P<0.001). In DCM compression model rats, IL-6 was elevated in CSF (40.5±3.3 vs. 13.2±2.4 pg/ml, P<0.001) and serum (7.1±1.7 vs. 2.9±1.6 pg/ml, P<0.001) samples from rats in the compression operation group compared with the sham operation group. Infusion of IL-6 in rats receiving the sham operation also led to motor function damage and mechanical allodynia threshold decline. CONCLUSIONS Serum IL-6 level was elevated in DCM patients and its concentration can predict symptom severity. Local infusion of IL-6 led to myelopathy symptoms in model rats, which suggests that anti-inflammation can effectively treat DCM.
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Project description:β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.
| S-EPMC7920360 | biostudies-literature
Project description:Background: An association between IL-6 levels and cytokine storm syndrome in COVID-19 patients has been suggested. Cases with higher IL-6 levels have more rapid progression and a higher complication rate. On the other hand, COVID-19 cases with anosmia have a milder course of the disease.Objective: We aimed to investigate whether there is a relationship between serum IL-6 levels and presence of anosmia in COVID-19 patients.Methods: Patients with a confirmed diagnosis of COVID-19 based on laboratory (PCR) were stratified into two groups based on presence of olfactory dysfunction (OD). In all cases with and without anosmia; psychophysical test (Sniffin' Sticks test) and a survey on olfactory symptoms were obtained. Threshold (t) - discrimination (d) - identification (i), and total (TDI) scores reflecting olfactory function were calculated. Clinical symptoms, serum IL-6 levels, other laboratory parameters, and chest computed tomography (CT) findings were recorded.Results: A total of 59 patients were included, comprising 23 patients with anosmia and 36 patients without OD based on TDI scores. Patients with anosmia (41.39 ± 15.04) were significantly younger compared to cases without anosmia (52.19 ± 18.50). There was no significant difference between the groups in terms of comorbidities, smoking history, and symptoms including nasal congestion and rhinorrhea. Although serum IL-6 levels of all patients were above normal values (7 pg/mL), patients with anosmia had significantly lower serum IL-6 levels (16.72 ± 14.28 pg/mL) compared to patients without OD (60.95 ± 89.33 pg/mL) (p = 0.026).Conclusion: Patients with COVID-19 related anosmia tend to have significantly lower serum levels of IL-6 compared to patients without OD, and the lower IL-6 levels is related to milder course of the disease. With the effect of low cytokine storm and IL-6 level, it may be said that anosmic cases have a milder disease in COVID-19.
| S-EPMC7591946 | biostudies-literature
Project description:Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells. Patients and Methods We treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine. Results The overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR+ cell level of 98/μL and those who did not achieve a remission had a median peak blood CAR+ cell level of 15/μL ( P = .027). High serum IL-15 levels were associated with high peak blood CAR+ cell levels ( P = .001) and remissions of lymphoma ( P < .001). Conclusion CAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.
| S-EPMC5455597 | biostudies-literature