Elevated Neopterin Levels Research Articles

Elevated neopterin and decreased IL-4, BDNF levels and depression in lymphoma patients receiving R-CHOP chemotherapy.

Depression is the most commonly observed psychological manifestation experienced by individuals diagnosed with cancer. The purpose of the study was to investigate the association between levels of IL-4, BDNF, neopterin, and depressive symptoms in lymphoma patients receiving consecutive cycles of chemotherapy. Newly diagnosed lymphoma patients scheduled to receive R-CHOP chemotherapy were enrolled. Effects of R-CHOP on circulatory biomarkers and depressive symptoms were assessed at three-time points [baseline assessment 7 days before the first dose of chemotherapy (TP1), interim assessment after the third cycle of chemotherapy (TP2), and follow-up assessment after the 6th cycle of chemotherapy (TP3)]. Seventy lymphoma patients, with a mean age of 44.17 ± 13.67 years, were enrolled. Patients receiving R-CHOP were found significantly increased neopterin levels between given time points TP1 vs. TP2, TP1 vs. TP3, and TP2 vs. TP3 (p < 0.001). However, IL-4 and BDNF levels significantly decreased with consecutive cycles of chemotherapy (p < 0.001). On Patient Health Questionnaire assessment (PHQ-9), scores of items like loss of interest, feeling depressed, sleep problems, loss of energy, and appetite problems were found significantly affected with consecutive cycles of chemotherapy (p < 0.001). The study found weak negative correlations between IL-4, BDNF, and neopterin levels and changes in PHQ-9 scores at both TP2 and TP3, suggesting a potential inverse relationship between these markers and depression symptoms. In conclusion, the present study suggests a potential link between elevated neopterin levels, decreased IL-4, and BDNF levels, and the presence of depression in lymphoma patients receiving R-CHOP chemotherapy. This study provides valuable insights into understanding the emotional challenges faced by cancer patients, offering information for more personalized interventions and comprehensive support approaches within the oncology setting.

Elevated NET, Calprotectin, and Neopterin Levels Discriminate between Disease Activity in COVID-19, as Evidenced by Need for Hospitalization among Patients in Northern Italy.

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful for discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining patients were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NETs), calprotectin, and DNase plasma levels via ELISA and a panel of proinflammatory cytokines via ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and do so more in hospitalized than non-hospitalized patients. C5a and sC5b-9, and other acute phase proteins, correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NETs, and neopterin are important proinflammatory parameters potentially useful for discriminating between COVID-19 patients at risk of hospitalization.

Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course

PurposePost-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.MethodsThe PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed.ResultsOur data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.ConclusionOur data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.

Cerebrospinal fluid biomarkers in SARS-CoV-2 patients with acute neurological syndromes.

Mechanisms underlying acute brain injury in SARS-CoV-2 patients remain poorly understood. A better characterization of such mechanisms remains essential to preventing long-term neurological sequelae. Our present aim was to study a panel of biomarkers of neuroinflammation and neurodegeneration in the cerebrospinal fluid (CSF) of NeuroCOVID patients. We retrospectively collected clinical and CSF biomarkers data from 24 NeuroCOVID adults seen at the University Hospital of Guadeloupe between March and June 2021. Among 24 NeuroCOVID patients, 71% had encephalopathy and 29% meningoencephalitis. A number of these patients also experienced de novo movement disorder (33%) or stroke (21%). The CSF analysis revealed intrathecal immunoglobulin synthesis in 54% of NeuroCOVID patients (two with a type 2 pattern and 11 with a type 3) and elevated neopterin levels in 75% of them (median 9.1nM, IQR 5.6-22.1). CSF neurofilament light chain (NfL) was also increased compared to a control group of non-COVID-19 patients with psychiatric illnesses (2905ng/L, IQR 1428-7124 versus 1222ng/L, IQR 1049-1566). Total-tau was elevated in the CSF of 24% of patients, whereas protein 14-3-3, generally undetectable, reached intermediate levels in two patients. Finally, CSF Aß1-42 was reduced in 52.4% of patients (median 536ng/L, IQR 432-904) with no change in the Aß1-42/Aß1-40 ratio (0.082, IQR 0.060-0.096). We showed an elevation of CSF biomarkers of neuroinflammation in NeuroCOVID patients and a rise of CSF NfL, evocative of neuronal damage. However, longitudinal studies are needed to determine whether NeuroCOVID could evolve into a chronic neurodegenerative condition.

Monocyte subsets display age-dependent alterations at fasting and undergo non-age-dependent changes following consumption of a meal

BackgroundMonocytes are a heterogenous population of immune cells whose subsets and functions become substantially dysregulated with advanced age. Although much of our current understanding of the age-related changes in monocytes is derived from fasting blood samples, most people are predominately in the postprandial state during waking hours. As hormonal, metabolic, and immunological changes in response to the consumption of a meal are manifested in postprandial blood, it’s unclear how age-dependent changes in peripheral monocytes at fasting are impacted by a dietary challenge.ObjectiveWe investigated the impact of age and meal consumption on circulating monocyte frequencies and subsets defined as classical (CD14 + CD16-), intermediate (CD14 + CD16 +), or non-classical (CD14dim CD16 +) in a cohort of 349 healthy adult volunteers grouped into categories based on their age: young adults (18–33 y, n = 123), middle adults (34–49 y, n = 115), and older adults (50–66 y, n = 111).ResultsFollowing 12-h fast total monocyte counts inversely correlated with subject age. Older adults had significantly fewer circulating monocytes along with elevated levels of TGs, cholesterol, glucose, IL-6, IL-8, TNF, neopterin, and CCL2 compared with young adults. Circulating monocyte pools in older adults consisted of smaller proportions of classical but larger proportions of intermediate and non-classical monocytes. Proportions of classical monocytes were inversely correlated with plasma TNF, IL-8, and neopterin while intermediate monocytes were positively correlated with plasma IL-6, TNF, and neopterin. Three hours after consuming a fat-containing meal postprandial monocyte counts increased in all age groups. Despite age-dependent differences in monocyte subsets at fasting, consumption of a meal induced similar changes in the proportions of classical and non-classical monocytes across age groups. Within the circulating postprandial monocyte pool, percentages of classical monocytes decreased while non-classical monocytes increased. However no change in precursory intermediate monocytes were detected. Our study confirms that ageing is associated with changes in monocyte frequencies and subsets and shows that consuming a fat-containing meal induces temporal changes in monocyte frequency and subsets independently of subject age.Clinical trialRegistered on ClincialTrials.gov (Identifier: NCT02367287)

Neopterin as a biomarker showing risks of developing pathology in bronchi and lungs among workers who have occupational contacts with industrial aerosols

Our research goal was to estimate neopterin level in blood serum of workers occupationally exposed to industrial aerosols with predominantly fibrogenic effects; to establish a relationship between this level and workers’ age, working experience in hazardous working conditions, spirometric parameters and the level of C-reactive protein. We also aimed to assess neopterin as a possible biomarker showing risks of the developing inflammatory process in the bronchi and lungs at its early stage. Our observation covered the following groups: workers employed at a metallurgic plant who had occupational contacts with industrial aerosols (exposure factors included welding and silicon-containing aerosols with predominantly fibrogenic effects in concentrations exceeding maximum permissible ones in workplace air); people suffering from chronic obstructive pulmonary disease of occupational etiology (COPD OE) in their post-exposure period; workers who didn’t have any occupational contacts with industrial aerosols. We determined neopterin contents in blood serum with ELISA test using “Neopterin ELISA” reagent kit (IBL, Hamburg). Elevated neopterin levels were detected in blood serum of 56.1 % workers who were occupationally exposed to industrial aerosols and 53.3 % of patients with COPD OE; we also found a direct correlation between levels of neopterin and interferon gamma. Only 18.7 % workers without any occupational contacts with industrial aerosols had elevated neopterin levels in their blood serum and there were no authentic correlations between these levels and interferon gamma contents in this group. Workers who were occupationally exposed to industrial aerosols had a more apparent increase in the average level of neopterin at an age younger than 40 years and working experience shorter than 20 years in comparison with workers without any such exposure. Neopterin can be used as a potential sensitive biomarker showing risks of an early inflammatory reaction in the lungs occurring in workers who are occupationally exposed to industrial aerosols. People with elevated neopterin levels in blood, especially those who are occupationally exposed to industrial aerosols, can be recommended to have their bronchi and lungs monitored in dynamics.

Неоптерин как биомаркер риска развития бронхолегочной патологии у работающих в контакте с промышленными аэрозолями Главные вкладки Просмотр(активная вкладка) Редактировать

Our research goal was to estimate neopterin level in blood serum of workers occupationally exposed to industrial aerosols with predominantly fibrogenic effects; to establish a relationship between this level and workers’ age, working experience in hazardous working conditions, spirometric parameters and the level of C-reactive protein. We also aimed to assess neopterin as a possible biomarker showing risks of the developing inflammatory process in the bronchi and lungs at its early stage. Our observation covered the following groups: workers employed at a metallurgic plant who had occupational contacts with industrial aerosols (exposure factors included welding and silicon-containing aerosols with predominantly fibrogenic effects in concentrations exceeding maximum permissible ones in workplace air); people suffering from chronic obstructive pulmonary disease of occupational etiology (COPD OE) in their post-exposure period; workers who didn’t have any occupational contacts with industrial aerosols. We determined neopterin contents in blood serum with ELISA test using “Neopterin ELISA” reagent kit (IBL, Hamburg). Elevated neopterin levels were detected in blood serum of 56.1 % workers who were occupationally exposed to industrial aerosols and 53.3 % of patients with COPD OE; we also found a direct correlation between levels of neopterin and interferon gamma. Only 18.7 % workers without any occupational contacts with industrial aerosols had elevated neopterin levels in their blood serum and there were no authentic correlations between these levels and interferon gamma contents in this group. Workers who were occupationally exposed to industrial aerosols had a more apparent increase in the average level of neopterin at an age younger than 40 years and working experience shorter than 20 years in comparison with workers without any such exposure. Neopterin can be used as a potential sensitive biomarker showing risks of an early inflammatory reaction in the lungs occurring in workers who are occupationally exposed to industrial aerosols. People with elevated neopterin levels in blood, especially those who are occupationally exposed to industrial aerosols, can be recommended to have their bronchi and lungs monitored in dynamics.

Clues to Disease Activity in Juvenile Dermatomyositis: Neopterin and Other Biomarkers.

Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker of macrophage activation. We included all JDM with neopterin data obtained before initiating medical therapy. We assessed T, B, NK cell populations, muscle enzymes, and disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), the duration of untreated disease, disease course, and myositis-specific antibody (MSA). Seventy-nine percent of 139 untreated JDM patients had elevated serum neopterin. The group with elevated neopterin had significantly more active disease: tDAS 11.9 vs. 8.1 (p < 0.0001), mDAS 5.8 vs. 3.1 (p < 0.0001), sDAS 6.1 vs. 4.9 (p = 0.0002), aldolase 24.0 vs. 7.6 U/L (p < 0.0001), von Willebrand factor antigen (p < 0.0001), and ESR 19.8 vs. 11.5 mm/hr (p = 0.01). The flow cytometry documented both reduced T cells (1494 vs. 2278/mm3, p = 0.008) and NK cells (145 vs. 240/mm3, p = 0.003). TNFα-308AA/AG polymorphism was more common in children with elevated neopterin than TNFα-308GG (p 0.05). We conclude that the availability of neopterin data will contribute to the rapid assessment of untreated JDM disease activity.

Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.

HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

Cerebrospinal fluid neopterin as a biomarker of treatment response to Janus kinase inhibition in Aicardi-Goutières syndrome.

Janus kinase (JAK) 1 inhibition represents a precision medicine approach in the treatment of Aicardi-Goutières syndrome (AGS), through targeting of type I interferon-mediated cell signalling. Blood interferon mRNAseq has been proposed as a biomarker of disease with utility in therapeutic monitoring. Objective cerebrospinal fluid (CSF) biomarkers tracking treatment efficacy are currently lacking. Here, we report a retrospective case series of 13 patients (median age 6y, range 2y 6mo-17y; five females, eight males) with AGS demonstrating significantly elevated CSF neopterin levels at first sampling (median 200nmol/L, range 45-2024nmol/L), compared to 13 age-matched controls with non-inflammatory neurological conditions (median 23nmol/L, range 5-34nmol/L, p<0.001). Five patients with AGS treated with JAK inhibitors demonstrated a median 81.5% reduction of CSF neopterin (range -36% to -88% change from baseline), compared to eight untreated patients with AGS demonstrating a median 7% reduction in CSF neopterin (range -63% to +117% change) (p=0.047). Our data indicate a biological effect of JAK inhibitors, and the potential role of CSF neopterin as a biomarker of treatment response.

Elevated levels of neopterin and pentraxin 3 in patients with rheumatoid arthritis.

As a systemic inflammatory disease, rheumatoid arthritis (RA) is the most common inflammatory arthritis in the population and there is no specific diagnostic marker in laboratory tests. The purpose of the study was to determine whether serum neopterin and pentraxin 3 (PTX3) levels may be a marker of increased inflammation in RA patients. The study were consist of 30 RA patients and 30 healthy controls who were admitted to the department of rheumatology. Blood specimens were taken from both group, and the levels of neopterin were analyzed by chromatography method (HPLC) and the PTX 3 levels were measured by enzyme-linked immunosorbent assay (ELISA). All data and demographic characteristics of participants were also recorded. Serum neopterin and PTX 3 levels of the patient group (25.99±7.24ng/mL and 4.19±1.01ng/dL, respectively) was higher than the control group (9.55±0.74ng/mL and 2.23±0.39ng/dL, respectively). These results were remarkable significant (p<0.01). No statistically significant correlation was found between age-PTX 3, age-neopterin and PTX 3-neopterin parameters in the patient group. In the control group, a significant negative correlation was found between age and PTX 3 (p<0.05), and a positive correlation between neopterin and PTX 3. Consequently, the serum neopterin and PTX 3 levels were higher in RA patients as compared to the healthy individuals. Our study suggest that there is a relation between neopterin and PTX 3 levels with RA patients. These findings suggest that neopterin and PTX 3 are important markers in the monitoring of RA disease.

Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activation.

Plant-based nutritional supplementation has been shown to attenuate and reduce mortality in the processes of both acute and chronic disorders, including diabetes, obesity, cardiovascular disease, cancer, inflammatory diseases, and neurological and neurodegenerative disorders. Low-level systemic inflammation is an important contributor to these afflictions and diets enriched in phytochemicals can slow the progression. The goal of this study was to determine the impact of lipopolysaccharide (LPS)-induced inflammation on changes in glucose and insulin tolerance, performance enhancement, levels of urinary neopterin and concentrations of neurotransmitters in the striatum in mouse models. Both acute and chronic injections of LPS (2 mg/kg or 0.33 mg/kg/day, respectively) reduced glucose and insulin tolerance and elevated neopterin levels, which are indicative of systemic inflammatory responses. In addition, there were significant decreases in striatal neurotransmitter levels (dopamine and DOPAC), while serotonin (5-HT) levels were essentially unchanged. LPS resulted in impaired execution in the incremental loading test, which was reversed in mice on a supplemental plant-based diet, improving their immune function and maintaining skeletal muscle mitochondrial activity. In conclusion, plant-based nutritional supplementation attenuated the metabolic changes elicited by LPS injections, causing systemic inflammatory activity that contributed to both systemic and neurological alterations.

Neopterin Predicts Disease Severity in Hospitalized Patients With COVID-19.

This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with coronavirus disease 2019 (COVID-19). Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for intensive care unit admission, need for mechanical ventilation, and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis

BackgroundMacrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF). AimsThis study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis. MethodsThis prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls. ResultsCirculating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002–1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000–1.004, p = 0.041), Child–Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan–Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001). ConclusionsHigher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.

FGF23 and Immune Activation are Correlated in Chronic Heart Failure and Additive Predictors of Poor Prognosis

Aims: Immune activation and disturbances of vitamin D metabolism are frequently encountered in patients with heart failure. Elevated fibroblast growth factor 23 (FGF23) levels as well as immune activation have been associated with a worse outcome in patients with heart failure. We evaluated the relationship of vitamin D metabolism and FGF23 levels with immune activation and its association with cardiac function and outcome in patients with heart failure. Methods and Results: In 149 patients with heart failure caused by nonischaemic cardiomyopathy, parameters of vitamin D metabolism (vitamin D, parathormone, phosphate, C-terminal FGF23, calcium), inflammation (hsCRP, neopterin) and cardiac function were investigated. Patients with elevated inflammatory parameters had significantly higher Ct-FGF23 levels (37.33 RU/mL vs. 17.60 RU/mL, p &lt; 0.001). The highest Ct-FGF23 and phosphate levels were found in patients with elevated neopterin and hsCRP levels as well as in in patients with progressive heart failure. Patients with high Ct-FGF23 and neopterin levels (Ct-FGF23 &gt; 22.60 RU/mL, neopterin &gt; 6.90 nmol/L) had a significantly higher risk for adverse events compared to patients with low Ct-FGF23 and neopterin levels (HR 7.386, [95%CI 2.543 – 21.447], p &lt; 0.001). Conclusions: Our study indicates a strong relationship of vitamin D metabolism, especially FGF23, with Th1 immune activation in patients with heart failure. Elevated Ct-FGF23 and neopterin levels are additive predictors for adverse cardiovascular events in patients with heart failure.

Meta-Analysis of HTLV-1-Infected Patients Identifies CD40LG and GBP2 as Markers of ATLL and HAM/TSP Clinical Status: Two Genes Beat as One.

Human T-lymphotropic virus 1 (HTLV-1) was the first recognized human retrovirus. Infection can lead to two main symptomatologies: adult T-cell lymphoma/leukemia (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Each manifestation is associated with distinct characteristics, as ATLL presents as a leukemia-like disease, while HAM/TSP presents as severe inflammation in the central nervous system, leading to paraparesis. Previous studies have identified molecules associated with disease development, e.g., the downregulation of Foxp3 in Treg cells was associated with increased risk of HAM/TSP. In addition, elevated levels of CXCL10, CXCL9, and Neopterin in cerebrospinal fluid also present increased risk. However, these molecules were only associated with specific patient groups or viral strains. Furthermore, the majority of studies did not jointly compare all clinical manifestations, and robust analysis entails the inclusion of both ATLL and HAM/TSP. The low numbers of samples also pose difficulties in conducting gene expression analysis to identify specific molecular relationships. To address these limitations and increase the power of manifestation-specific gene associations, meta-analysis was performed using publicly available gene expression data. The application of supervised learning techniques identified alterations in two genes observed to act in tandem as potential biomarkers: GBP2 was associated with HAM/TSP, and CD40LG with ATLL. Together, both molecules demonstrated high sample-classification accuracy (AUC values: 0.88 and 1.0, respectively). Next, other genes with expression correlated to these genes were identified, and we attempted to relate the enriched pathways identified with the characteristic of each clinical manifestation. The present findings contribute to knowledge surrounding viral progression and suggest a potentially powerful new tool for the molecular classification of HTLV-associated diseases.

Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis.

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n = 24) as compared to multiple sclerosis (MS, n = 61) and control (n = 19) groups. Detailed clinical pictures of patients are presented. We focused on relevant cerebrospinal fluid (CSF) tests like protein levels, cytosis and oligoclonal bands, neuroinflammation indices (interleukin-6, soluble receptor of IL-6, neopterin, anti-ribosomal proteins antibodies) and markers of neurodegeneration (phosphorylated neurofilament heavy chain, pNfh). Elevated neopterin level was found in AE group as compared to the MS and control groups, while protein and pNfh were increased in both AE and MS groups. In the MS group, the cytosis and soluble receptor of IL-6 were higher as compared to the control group. Anti-ribosomal proteins antibodies were increased in a single patient with AE. High levels of protein were predictive of mortality in AE patients, while IL-6 and pNfh were elevated in severe AE patients. AE patients with paraneoplastic etiology demonstrated oligoclonal bands positivity. Taken together, our results suggest the neopterin as an additional marker of autoimmune brain inflammation. Though higher levels of protein, IL-6 and pNfh were found in patients with severe disease progression and death, prognostic values of these markers should be validated in larger cohorts of patients.

Elevated neopterin levels in wild, healthy chimpanzees indicate constant investment in unspecific immune system

BackgroundEcological immunology proposes that the optimal immune defence, and the costs coming with it, vary across environments. In environments with higher pathogen load, the immune system should experience greater challenges and, therefore, investment in maintaining it should be higher. The biomarker neopterin allows monitoring of innate immune responses, and is therefore an ideal tool to investigate the effects of ecological variables on the immune system. Here, we compared urinary neopterin levels of apparently healthy chimpanzees without acute symptoms of sickness across two environments: in captivity (22 zoos) and in the wild (two populations).ResultsOur results revealed that urinary neopterin levels were nearly twice as high in wild compared to captive chimpanzees, independent of chimpanzee subspecies.ConclusionWe conclude that wild chimpanzees experience more frequent immune challenges in comparison to captive individuals. Therefore, wild individuals have to allocate more energy to immune function and away from reproduction and growth. Our data indicate that the generally delayed development of wild animals in comparison to captive individuals might not only be related to lower energy intake but might result from greater energy allocations to immune function. Finally, our data highlight the importance of understanding immune costs for accurate characterization of energy budgets in animals.

ATAXIA AS A PRESENTING SYMPTOM OF IMMUNE DYSREGULATION DISORDER IN THE SETTING OF EBV INFECTION

Introduction Epstein-Barr virus usually leads to mild, self-limiting infection in immunocompetent host. However, patients with defective cell-mediated cytotoxicity can get life-threatening infection with Hemophagocytic Lymphohistiocytosis features. Case Description 2-year-old Hispanic girl presented with acute onset of ataxia and slurry speech. No fever or lymphadenopathy were noted. CSF EBV PCR was positive and her MRI was consistent with viral encephalitis. She was treated with IVIG, steroids, and Acyclovir for 2 weeks. Over the next few months, her symptoms started to worsen again to the point that she could not sit up. Her MRI showed worsening of the inflammation with new hemorrhagic lesions. Brain biopsy was positive EBV DNA in situ hybridization and showed T cell and histiocytic infiltration. Her immunological evaluation revealed a mild reduction in T and NK cells number, normal B cells count, and normal immunoglobulin levels. HIV PCR was negative. SAP expression was normal; however, NK cell function was absent. HLH evaluation was unremarkable except for elevated serum and CSF neopterin levels. She was treated with steroid in addition to rituximab (IV and then intrathecally) to decrease the EBV viral load (fig1). Few weeks later, the Genetic test revealed a missense homozygotic mutation of perforin gene (c.1337A>C) which is validated by flow cytometry. With a diagnosis of primary HLH confirmed, the patient was treated with etoposide waiting for matched donor bone marrow transplant. Discussion NK cells disorders should be considered in pediatric patients with severe or unusual EBV infection. Rituximab is effective in decreasing EBV viral load.

Clinical Value of Serum Neopterin in Breast Cancer

Background: The immune marker neopterin may have a prognostic role in different cancers including breast cancer. Aim: To assess the relation between pre-chemotherapy serum level of neopterin and the clinical and pathological features of breast cancer patients. Methods:Sixty-three patients with histologically confirmed breast cancer and 20 healthy females matched for age and sex as controls were included. All patients were subjected to full history taking, thorough medical examination and complete investigation. Venous blood samples were collected from all participants to measure serum neopterin level. Serum neopterin level more than 10 nMolL was considered elevated. Results: The mean serum neopterin level among patients was 8 ± 7.43. Twenty-two patients (34.9%) had elevated serum neopterin level. Neopterin was found to be significantly elevated in patients with advanced stages and grade III tumors. Metastatic disease was associated with significantly higher levels of neopterin (p = 0.04). There was no significant association between high neopterin level and mean time to progression or overall survival. Conclusion:Among breast cancer patients, the immune marker neopterin was significantly related to metastatic disease and it could be considered a potential marker for systemic spread of the tumor.