Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1β, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the “cytokine storm” occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.

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Toll-like receptors 2, 4 and 7, interferon-gamma and interleukin 10, and programmed death ligand 1 transcripts in skin from dogs of different clinical stages of leishmaniosis

Parasites & Vectors ◽

10.1186/s13071-019-3827-7 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 3

Author(s):

Laura Ordeix ◽

Sara Montserrat-Sangrà ◽

Pamela Martínez-Orellana ◽

Marta Baxarias ◽

Laia Solano-Gallego

Keyword(s):

Immune Response ◽

Disease Severity ◽

Interferon Gamma ◽

Expression Profiles ◽

Severe Disease ◽

Disease Stage ◽

Canine Leishmaniosis ◽

Toll Like Receptors ◽

Cutaneous Lesions ◽

Ifn Γ

Abstract Background Canine leishmaniosis (CanL) caused by Leishmania infantum can have several dermatological manifestations. The type of immune response elicited against the parasite appears to be at the basis for such clinical variability. Much of the work in CanL has focused on adaptive immune response and there are scarce data on the importance of the innate immune responses. Moreover, few studies have evaluated the immunological response in the cutaneous lesions in dogs naturally infected with L. infantum and with different degrees of disease severity, and no study has compared clinically-lesioned with normal-looking skin. Methods We determined and compared the transcription of toll like receptors (TLRs) 2, 4 and 7, interferon gamma (IFN-γ), interleukin (IL) 10 and programmed cell death protein ligand (PD-L) 1 by real-time PCR in paired clinically-lesioned and normal-looking skin from 25 diseased dogs (mild disease-stage I (n = 11) and moderate to severe disease-stages II and III (n = 14) as well as in normal-looking skin from healthy dogs (n = 10) from a non-endemic area. We also assessed the association between the transcripts in clinically-lesioned and normal-looking skin of dogs with leishmaniosis with clinicopathological, immunological and parasitological findings. Results Clinically-lesioned skin from mildly affected dogs was characterized by a significant upregulation of TLR2 (P < 0.0001) and IL-10 (P = 0.021) and downregulation of TLR7 (P = 0.004) when compared with more severely affected dogs. Normal-looking skin of mildly affected dogs was characterized by a significant lower expression of TLR7 (P = 0.003), IFN-γ (P < 0.0001) and PD-L1 (P = 0.001) when compared with more severely affected dogs. TLR2, TLR4, IL-10 and IFN-γ upregulation in clinically-lesioned skin was correlated with lower disease severity while TLR7 upregulation was correlated with markers of disease severity. Upregulation of TLR7, IL-10, IFN-γ and PD-L1 in normal-looking skin was correlated with disease severity. Conclusions This study demonstrated different expression profiles of immune genes in clinically-lesioned and normal-looking skin among mildly and more severely affected dogs. These immunological conditions might favor the maintenance and replication of the parasite in the skin of more severely affected dogs.

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JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽

10.3390/biom11071059 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1059

Author(s):

Yu-Tsai Lin ◽

Wei-Chih Chen ◽

Ming-Hsien Tsai ◽

Jing-Ying Chen ◽

Chih-Yen Chien ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Disease Severity ◽

Nasal Polyps ◽

Inflammatory Diseases ◽

Janus Kinase ◽

Sinus Surgery ◽

Control Group ◽

Jak2 Inhibitor ◽

Ifn Γ ◽

Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

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Vitamin D deficiency in adult patients with ulcerative colitis: Prevalence and relationship with disease severity, extent, and duration

Indian Journal of Gastroenterology ◽

10.1007/s12664-019-00932-z ◽

2019 ◽

Vol 38 (1) ◽

pp. 6-14 ◽

Cited By ~ 3

Author(s):

Arjun Datt Law ◽

Usha Dutta ◽

Rakesh Kochhar ◽

Chetana Vaishnavi ◽

Shiva Kumar ◽

...

Keyword(s):

Ulcerative Colitis ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Disease Severity ◽

Adult Patients

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Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling

Blood ◽

10.1182/blood-2002-03-0697 ◽

2003 ◽

Vol 101 (1) ◽

pp. 216-225 ◽

Cited By ~ 18

Author(s):

Anthony D. Cristillo ◽

Mirtha J. Macri ◽

Barbara E. Bierer

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Signaling Pathways ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Expression Profiles ◽

Lymphoid Tissues ◽

Rnase Protection ◽

Chemokine Expression ◽

Calcineurin Activity

Abstract The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.

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The Ability to Use Epinephrine Autoinjector in Patients Who Receive Prescription Immediately after Anaphylaxis

International Archives of Allergy and Immunology ◽

10.1159/000513421 ◽

2021 ◽

pp. 1-6

Author(s):

Saša Kadivec ◽

Mitja Košnik

Keyword(s):

Higher Education ◽

Shelf Life ◽

Anaphylactic Reaction ◽

Family Physician ◽

Fatal Outcome ◽

Education Level ◽

Adult Patients ◽

Prescription Rate ◽

Training Device ◽

Epinephrine Autoinjector

Background: Epinephrine autoinjector (EAI) is prescribed to prevent a fatal outcome in the case of a repeated anaphylactic reactions. We wanted to determine how adult patients who received their first prescription as part of an urgent treatment of an anaphylactic reaction or at their family physician were instructed on the use of EAI. Methods: Nurses assessing patients’ knowledge asked the patient to demonstrate how to use the EAI training device. Patients who performed the critical steps correctly in 1 min were labelled as competent. Results: Forty-one patients (24% women, 46 ± 5 years) came for the allergy examination 116 ± 145 days after receiving a prescription for EAI. When prescribing, the doctor or nurse explained the instructions for the use of EAI to 63.4% patients, and 31.7 patients practiced the use of EAI using a training device. At the pharmacy, 22% received explanation and 7% also practiced using a training device. Fifty-four percent of patients were able to effectively administer EAI adrenaline within 1 min. Higher education level was associated with sufficient knowledge about the use of EAI (p = 0.026). At the time of the visit to the allergy specialist clinic, 61% of patients had EAI with them. The shelf life of EAI was known to 63% of patients. Conclusions: The activities to increase the prescription rate of EAI immediately after treatment of anaphylactic episode are not sufficient to prevent severe outcome after the repeated episodes of anaphylaxis as nearly a half of patients are not able to use EAI correctly.

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Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity

Multiple Sclerosis Journal ◽

10.1177/1352458518819380 ◽

2018 ◽

Vol 26 (2) ◽

pp. 210-219 ◽

Cited By ~ 16

Author(s):

Heidi Högel ◽

Eero Rissanen ◽

Christian Barro ◽

Markus Matilainen ◽

Marjo Nylund ◽

...

Keyword(s):

Multiple Sclerosis ◽

Nervous System ◽

Glial Fibrillary Acidic Protein ◽

Disease Progression ◽

Disease Severity ◽

Single Molecule ◽

Progressive Disease ◽

Disease Duration ◽

Acidic Protein ◽

Csf Levels

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels. Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS. Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison. Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology. Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.

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Local production of CCL3, CCL11, and IFN-γ correlates with disease severity in murine parainfluenza virus infection

Virology Journal ◽

10.1186/1743-422x-10-357 ◽

2013 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Manika Suryadevara ◽

Cynthia A Bonville ◽

Helene F Rosenberg ◽

Joseph B Domachowske

Keyword(s):

Virus Infection ◽

Disease Severity ◽

Parainfluenza Virus ◽

Local Production ◽

Ifn Γ

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Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients (HEMICU): a prospective observational study protocol

BMJ Open ◽

10.1136/bmjopen-2019-032695 ◽

2019 ◽

Vol 9 (10) ◽

pp. e032695 ◽

Cited By ~ 3

Author(s):

Gunnar Lachmann ◽

Cornelia Knaak ◽

Clarissa von Haefen ◽

Nadine Paeschke ◽

Christian Meisel ◽

...

Keyword(s):

Incidence Rate ◽

Critically Ill ◽

Critically Ill Patients ◽

Fatal Outcome ◽

Experimental Studies ◽

Ethics Committee ◽

Adult Patients ◽

Haemophagocytic Lymphohistiocytosis ◽

Diagnostic Biomarkers ◽

Potential Biomarker

IntroductionHaemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated.Methods and analysisThe HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité – Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine.Ethics and disseminationThe institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité – Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences.Trial registration numberNCT03510650.

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Not Only High Number and Specific Comorbidities but Also Age Are Closely Related to Progression and Poor Prognosis in Patients With COVID-19

Frontiers in Medicine ◽

10.3389/fmed.2021.736109 ◽

2022 ◽

Vol 8 ◽

Author(s):

Dafeng Liu ◽

Yongli Zheng ◽

Jun Kang ◽

Dongmei Wang ◽

Lang Bai ◽

...

Keyword(s):

Clinical Trial ◽

Disease Progression ◽

Disease Severity ◽

Poor Prognosis ◽

Chronic Obstructive ◽

Clinical Trial Registry ◽

Alcoholic Fatty Liver ◽

Clinical Type ◽

Conversion Time ◽

Negative Conversion

Background: Some patients with comorbidities and rapid disease progression have a poor prognosis.Aim: We aimed to investigate the characteristics of comorbidities and their relationship with disease progression and outcomes of COVID-19 patients.Methods: A total of 718 COVID-19 patients were divided into five clinical type groups and eight age-interval groups. The characteristics of comorbidities were compared between the different clinical type groups and between the different age-interval groups, and their relationships with disease progression and outcomes of COVID-19 patients were assessed.Results: Approximately 91.23% (655/718) of COVID-19 patients were younger than 60 years old. Approximately 64.76% (465/718) had one or more comorbidities, and common comorbidities included non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes mellitus (DM), chronic hepatitis B (CHB), hyperuricaemia, and gout. COVID-19 patients with comorbidities were older, especially those with chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Hypertension, DM, COPD, chronic kidney disease (CKD) and CVD were mainly found in severe COVID-19 patients. According to spearman correlation analysis the number of comorbidities was correlated positively with disease severity, the number of comorbidities and NAFLD were correlated positively with virus negative conversion time, hypertension, CKD and CVD were primarily associated with those who died, and the above-mentioned correlation existed independently of age. Risk factors included age, the number of comorbidities and hyperlipidaemia for disease severity, the number of comorbidities, hyperlipidaemia, NAFLD and COPD for the virus negative conversion time, and the number of comorbidities and CKD for prognosis. Number of comorbidities and age played a predictive role in disease progression and outcomes.Conclusion: Not only high number and specific comorbidities but also age are closely related to progression and poor prognosis in patients with COVID-19. These findings provide a reference for clinicians to focus on not only the number and specific comorbidities but also age in COVID-19 patients to predict disease progression and prognosis.Clinical Trial Registry: Chinese Clinical Trial Register ChiCTR2000034563.

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4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis

Journal of Neuroinflammation ◽

10.1186/s12974-021-02143-w ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Wen-Tsan Weng ◽

Ping-Chang Kuo ◽

Dennis A. Brown ◽

Barbara A. Scofield ◽

Destin Furnas ◽

...

Keyword(s):

Autoimmune Disease ◽

Experimental Autoimmune Encephalomyelitis ◽

Immune Responses ◽

Disease Progression ◽

Disease Severity ◽

Autoimmune Encephalomyelitis ◽

Relapsing Remitting ◽

Th17 Differentiation ◽

Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. Methods Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. Results Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. Conclusions Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.

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