Neopterin In Patients Research Articles

Investigation of neopterin levels in children with hashimoto thyroiditis

ABSTRACT Objective: Hashimoto Thyroiditis is an autoimmune disease caused by genetic and environmental factors and is known as the most common cause of hypothyroidism in childhood. Neopterin has been measured in many autoimmune disorders and has been identified as a marker of cellular immune activation. The aim of this study was to investigate the autoimmune association of neopterin in patients with Hashimoto's Thyroiditis aged 5-18 years. Material and Method: Neopterin levels were measured in 80 individuals, 40 of whom were followed up with the diagnosis of Hashimoto Thyroiditis and 40 of whom were not diagnosed with Hashimoto Thyroiditis. Results: While the mean value of neopterin levels in the control group participating in this study was 86.4170 ± 3.59284, the mean value in the patient group was 101.32 ± 9.75378. When we look at the participant age data, it is seen that the patients and controls are compatible with each other (p>0.05). In addition, it is seen that there is a significant positive correlation p

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions

Background and objectiveEndothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients.MethodsA total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro.ResultsEndothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05).ConclusionNP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

The concentration of serum neopterin in patients with surgical treatment of spondyloarthrosis complicated byfacet syndrome

Objective. To study the concentration of serum neopterin in patients before and after surgical treatment of pain syndrome caused by the formation of facet syndrome associated with spondyloarthrosis. Materials and methods. The study involved 52 patients (32 men and 20 women) hospitalized to the neurosurgical department of the City Clinical Hospital No. 4. The main group consisted of 26 patients with spondyloarthrosis complicated by chronic pain associated with facet syndrome. The comparison group (n=26) consisted of patients with pain syndrome in radiculopathy. The control group (comparable in gender and age) consisted of 10 people who underwent periodic examination. The concentration of neopterin in blood serum was determined by solid-phase enzyme immunoassay (ELISA) using the Neopterin ELISA kit (cat. No. 59321; lot ENO230) ("IBL", Germany). Results. Statistically significant differences in the level of serum neopterin concentration (p = 0.0016) were revealed between the studied groups. The highest concentration of neopterin was noted in the comparison group, where it was 10.31 ± 2.02 nmol/l, exceeding the results of the control group (p=0.02256) and the main group (p=0.04996). Three months after surgical treatment of patients in the main group, the median content of serum neopterin decreased by 1.161 times (p = 0.049029). Conclusion. Further studies to clarify the influence of pain on metabolic processes and neopterin in particular are required.

Assessment of Serum Neopterin Levels in patients hospitalized with severe COVID-19

Background: COVID-19 has caused a considerable number of hospital admissions in China since December 2019. Many COVID-19 patients experience signs of acute respiratory distress syndrome, and some are even in danger of dying. Objective: to measure the serum levels of D-dimer, Neutrophil-Lymphocyte count ratio (NLR), and neopterin in patients hospitalized with severe COVID-19 in Baghdad, Iraq. And to determine the cut-off values (critical values) of these markers for the distinction between the severe patients diagnosed with COVID‐19 and the controls. Materials and methods: In this case-control study, we collect blood from 89 subjects, 45 were severe patients hospitalized in many Baghdad medical centers who were diagnosed with COVID-19 infection, and 44 were apparently healthy subjects as a control. The time of collection is from September 15 th to December 31 th, 2021. The optimal cut-off points (critical values) and prognostic relevance of D-dimer, Neutrophil-Lymphocyte count ratio (NLR), and neopterin were investigated using (ROC) curves analysis. Results: In severe patients hospitalized with COVID-19 the levels of D-dimer, NLR, and neopterin were statistically significantly higher than in control participants (P&lt; 0.005). The D-dimer, NLR, and neopterin tests have areas under the receiver operating characteristic (ROC) curves of 0.920, 0.90, and 0.74 respectively, and their critical values for the differentiation between the severe patients and control were 0.22 μg/ml, 2.56, and 3.02 nmol/L. Conclusions: D-dimer, NLR, and neopterin levels in sever COVID-19 patients were higher than control, with values of greater than 0.22μg/ml, 2.56 and 3.02nmol/L respectively was linked to a severe COVID-19infection with good sensitivity and selectivity.

Маркери імунного запалення у хворих на неалкогольну жирову хворобу печінки коморбідну із хронічним обструктивним захворюванням легень

The purpose of the study was to determine markers of immune inflammation in patients with nonalcoholic fatty liver disease combined with chronic obstructive pulmonary disease. Materials and methods. The observation revealed 82 patients who were treated in the pulmonology and gastroenterology department of the Andriy Novak Transcarpathian Regional Clinical Hospital during 2018-2020 with a diagnosis of nonalcoholic fatty liver disease and chronic obstructive pulmonary disease II group B and C. Among the examined there were 61.0% (50) men and 40.0% (32) women. The average age was 57.8±1.5 years old. Results and discussion. As a result of the conducted research it is established that increased levels of chronic immune inflammation markers were observed in all examined with significant increase in patients with a comorbid condition. The highest concentrations of C-reactive protein were found in patients with nonalcoholic fatty liver disease combined with chronic obstructive pulmonary disease with frequent exacerbations and hospitalization, and exceeded the normal values by 8.3 times. The levels of tumor necrosis factor-α and neopterin in patients with frequent exacerbations of chronic obstructive pulmonary disease and hospitalization were by 2.7 times and 1.9 times higher than in patients with a small number of exacerbations and by 3.2 and 3.9 times higher than in patients with nonalcoholic fatty liver disease without chronic obstructive pulmonary disease. The indexes of interleukin-6, transforming growth factor-β, the number of IgG antibodies to neutrophil elastase and the level of tissue inhibitor of matrix proteinases-1 remain consistently high in all patients with combined pathology of nonalcoholic fatty liver disease and chronic obstructive pulmonary disease regardless of the frequency of exacerbations, thus supporting inflammation even in remission. Elastase antibody levels correlate directly with the levels of the tissue metalloproteinase-1 inhibitor and increase with the degree of severety of fibrosis, which may indicate a high level of serum neutrophil elastase activity in patients with nonalcoholic fatty liver disease in combination with chronic obstructive pulmonary disease and its participation in fibrosis. Conclusion. Patients with nonalcoholic fatty liver disease in combination with chronic obstructive pulmonary disease showed an increased level of chronic systemic inflammation of low intensity based on the analysis of C-reactive protein, tumor necrosis factor-α, neopterin and interleukin-6 compared with nonalcoholic fatty liver disease without chronic obstructive pulmonary disease even in remission, which indicates an aggravating course of the disease in combination of two pathologies. Stably high concentration of IgG antibodies to neutrophil elastase may indirectly indicate the maintenance of the activity of this enzyme in the serum of patients with nonalcoholic fatty liver disease in chronic obstructive pulmonary disease and confirms its participation in liver fibrogenesis

Serum neopterin levels and their role in the prognosis of patients with ischemic stroke: A systematic review and meta-analysis

BackgroundNeopterin is an inflammatory marker that is found to have prognostic value in cardiovascular diseases but its prognostic role in cerebrovascular diseases is not as clear. This study evaluates the prognostic role of neopterin in patients with ischemic stroke. MethodStudies were identified after a literature search in electronic databases (Ovid, PubMed, Science Direct, and Wiley) and were selected based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate mean difference in blood neopterin levels between ischemic stroke patients and healthy individuals or between severe and low/moderate ischemic stroke. Prognostic information contained in research articles of included studies was synthesized. ResultsFourteen studies (1823 ischemic stroke patients and 2189 healthy individuals) were included. Serum neopterin levels were 4.22 ng/ml [95% confidence interval (CI): 3.66, 4.77] in ischemic stroke patients and 1.80 ng/ml [95% CI: 1.13, 2.46] in normal individuals (mean difference 2.14 ng/ml [95% CI: 1.41, 2.87]; p < 0.00001). Neopterin levels were significantly higher in patients with severe than in low/moderate ischemic stroke (mean difference 1.36 ng/ml [95% CI: 0.58, 2.13]; p = 0.0006). In individual studies, higher serum neopterin levels were found to be predictive of secondary stroke, adverse clinical or functional outcomes, depression, and mortality. Neopterin levels correlated positively with high-sensitivity c reactive protein (hsCRP), National Institutes of Health Stroke Scale score, and infarct volume. ConclusionBlood neopterin levels are found significantly higher in ischemic stroke patients and correlated positively with hsCRP, disease severity, and infarct volume. Higher neopterin levels are associated with a worse prognosis of ischemic stroke.

Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia

Background and aimsPatients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients. MethodsThe study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups. ResultsCompared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = −0.54, p = 0.001), high-sensitivity CRP (r = −0.53, p = 0.001), HOMA-IR (r = −0.31, p = 0.01), CA-IMT (r = −0.22, p < 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = −0.22, p < 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001). ConclusionsOur study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

Serum Neopterin Levels and the Clinical Presentation of COVID-19

AbstractIn Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) &gt; 2.8 compared to those with a dNLR ≤ 2.8 (p&lt; 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis.

Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon-γ and is considered as a marker for macrophage activation. This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty-two consecutive DM patients and 30healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P<0·001). High serum neopterin levels were associated with anti-melanoma differentiation-associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP-ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β=30·24, P<0·001). In addition, a significant increase in serum neopterin concentration of non-survivors was observed when compared to that of survivors (P<0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non-survivors and survivors at an optimal cut-off level of 22·1nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P<0·001). Kaplan-Meier survival curves revealed that DM patients with serum neopterin >22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin<22·1nmol/l (log-rank P<0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio=4·619, 95% confidence interval=2·092-10·195, P<0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP-ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.

High level of anti-helicobacter pylori-heat shock protein 60II3, interferon-γ, and neopterin are risk factors of cardiovascular events in acute coronary syndrome patients

Background: Chronic inflammatory process that may cause acute myocardial infarction (AMI) has been known to play an important role in the pathogenesis of atherosclerosis and atheroma plaque instability. Based on inflammation process, several previous studies showed contradictory results in finding a relationship between infection H. pylori with the formation of atherosclerosis through the establishment of immunoglobulin G (IgG) anti-H. pylori-HSP60II3 (IgG anti-Hp-HSP60II3), and neopterin level due to oxidative stress. This study aims to know whether IgG anti-Hp-HSP60II3, IFN-γ and neopterin are risk factors of cardiovascular events (CVE) in patients with ACS.Methods: A prospective cohort study was conducted among 66 patients to determine the levels of IgG anti-Hp-HSP60II3, IFN-γ, and neopterin in patients with ACS as well as the levels of IgG anti-Hp-HSP60II3, IFN-γ, and neopterin. ACS patients were grouped into two groups: patients with ACS with positive prognostic factors (high levels of IgG anti-Hp-HSP60II3, IFN-γ, neopterin, and hs-CRP) and the group of patients with ACS without prognostic factor (low level of anti-IgG levels hp-HSP60II3, IFN-γ, neopterin, hs-CRP), and then were observed for 6 months while in the hospital. Data were analyzed using SPSS version 20 for Windows.Results: In observations over a period of 6 months, found as many as 15 (22.7%) patients with CVE, which consisted of 11 (16.7%) patients’ vascular death, 3 (4.5%) patients had IMA and 1 (1.5%) patients experienced recurrent cardiac ischemia from 66 patients with ACS. Mean difference between the time of occurrence CVE subjects with high and low levels of neopterin are statistically significant (P&lt;0.05). When confounding factors such as dyslipidemia, diabetes, hypertension, obesity, smoking, and age are controlled, only neopterin levels affect the incidence CVE with the incidence rate ratio of 6.46 (95% CI: 1.45-28.74; p = 0.014) and path analysis found the effect of neopterin on CVE incidence about 49,1%, p &lt; 0.05. Kaplan-Meier analysis gives result that the average time of CVE on a group of subjects with high levels of neopterin is shorter (129.09 days) than the group of subjects with low levels of neopterin (168.33 days) (P=0.008).Conclusion: This study found that the high level of anti-helicobacter pylori-heat shock protein 60II3, interferon-γ, and neopterin have a potential role in predicting risk factors of cardiovascular events in acute coronary syndrome patients

Positive effect of ozonotherapy on serum concentration of soluble interleukin-2 receptor and neopterin in patients with systemic sclerosis.

IntroductionSystemic sclerosis (SSc) is a chronic systemic autoimmune disease of unknown aetiology. No curative therapy exists, thus management includes controlling of symptoms and prevention of complications. Ozonotherapy has multiple beneficial therapeutic effects which can translate into improving prognostic factors for SSc.AimTo evaluate the effect of ozone on selected factors of inflammation: serum concentration of the soluble receptor of interleukin-2 (IL-2 sR), neopterin as well as the peripheral blood smear in patients with SSc.Material and methodsForty-two patients with SSc underwent two series of 10-minute baths in water with a mixture of air and ozone separated by a 10-day period without treatment. Examinations were performed at baseline and 10 days after completing the last treatment.ResultsThe mean concentration of IL-2 sR decreased significantly from 1563.73 to 1249.86 pg/ml. The mean concentration of neopterin decreased significantly from 12.06 to 10.9 nmol/ml. Absolute monocytosis decreased insignificantly from 1.694 to 1.480 G/l. Correlations between the disease duration and concentration of IL-2 sR were weak and negative, while between the disease duration and concentration of neopterin were weak and positive.ConclusionsOzonotherapy had a beneficial influence on the immune response in patients with scleroderma. Balneotherapy may be considered as an additional therapeutic option, but further research is required.

Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes.

SummaryBackgroundAn increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence.MethodsThe study included a total of one hundred thirtynine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay.ResultsSerum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p<0.001).ConclusionsEarly diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

Correlation of Serum Neopterin level with Complement C3, C4 in assessment of Systemic Lupus Erythematosus Activity

Background: Systemic lupus erythematosus (SLE) has a recurrent disease activity throughout the natural course of the disease. Assessment of this activity is often complex and time consuming. To date no measures have been created specifically for SLE. Studying serum neopterin and comparing it with other established parameters C3, C4 may add benefit for SLE follow up. Aim: The aim of our study is to evaluate the level of serum neopterin in patient with systemic lupus erythematosus (SLE) as a marker of disease activity and its correlation with other parameters of disease activity. Patients and methods: Seventy five subjects; 60 patients with (SLE); 30 of them are active and another 30 with no activity and 15 healthy subjects as a control group. Results: Serum neopterin was higher in the active group than the inactive group and a significant difference between the patients with SLE group than controls group was also reported.Our results shows thatthe mean value of serum neopterin in whole SLE patients (21.9 ng/ml)and the serum neopterin in the active and inactive groups was 33.9 ng/ml and 3.45 ng/ml respectively which were highly significant than the mean value of the control group (P<0.001).Also the differences between the three groups was highly significant (P<0.001). Conclusion: As increased serum neopterin levels were found in patients with SLE and were correlated with certain clinical and laboratory immunoinflammatory parametersthen estimation of serum neopterin levels seems beneficial in the assessment of disease activity and evaluation of the efficacy of various treatment regimens used.

Clinical and prognostic value of determining the level of neopterin in patients with chronic heart failure with preserved ejection fraction

Objective: to analyze the level of neopterin in patients with chronic heart failure (CHF) with a preserved fraction ejection fraction depending on the stage of the disease. Materials and methods: were examined 148 patients with CHF with preserved ejection fraction (50% and &gt;) and 30 as a control group. Patients with CHF were divided into groups depending on the stage of CHF (from I to III). The level of neopterine was determined by the method of enzyme immunoassay in blood plasma. Results: in patients with CHF with preserved ejection fraction there was a tendency to increase the level of neopterin from stage I to stage III compared to the control group. In the group of patients with CHF IIB+III the level of neoplasm was statistically slightly lower compared to patients of stage I and IIA, but statistically signifi cantly higher than in the control group. Conclusion: it was revealed the change in the level of neopterin in patients with CHS with retained ejection fraction depending on the stage of the disease.

Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes

Summary Background: An increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence. Methods: The study included a total of one hundred thirty-nine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. Results: Serum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p&lt;0.00001). Conclusions: Early diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

NEOPTERIN DAN PEROKSIDA SERUM SEBAGAI PETANDA MAKROFAG TERAKTIVASI PADA TUBERKULOSIS PARU AKTIF DAN INDIVIDU BERKEBAHAYAAN TINGGI (Serum Neopterin and Peroxide As Marker of Activated Macrophages on Active Pulmonary Tuberculosis and Individuals At High Risk)

Failure of macrophages to phagocytize Mycobacterium tuberculosis causes the release of hydrogen peroxide/peroxide (H2O2) bythe activated macrophages. Neopterin is one of the most important markers in the activated macrophages. Neopterin is a pteridinederivative produced by the activated macrophages through the stimulation of interferon gamma. Increased levels of Neopterin has beenreported in lung tuberculosis. Activation of macrophages is essential to the development of tuberculosis infection that can lead to activepulmonary tuberculosis or latent tuberculosis, in this case is a high-risk for healthy individuals. To determine the differences in serumlevels of Neopterin and H2O2 between patients with active pulmonary tuberculosis and healthy individuals at high risk of pulmonarytuberculosis. A total of 15 patients with active pulmonary tuberculosis and 15 healthy individuals at high risk examination serumNeopterin levels and peroxide (H2O2). Active pulmonary tuberculosis patients when the results of sputum smear examination chest x-raysis obtained positive results. Healthy individuals at high risk when the results of smear examination and chest x-rays is negative. Thelevel of Neopterin was examined using a double antibody sandwich immunoassay with Human neopterin (NEOP) ELISA Kit ® BioassayTechnology Laboratory. The level of peroxide was examined using quantitative colorimetric peroxidedetermination with QuantiChromTMPeroxide Assay Kit (DIOX-250)®. Neopterin serum levels between patients with active pulmonary tuberculosis and healthy individualsat high-risk were analysed by independent samples t-test. H2O2 serum levels between patients with active pulmonary tuberculosis andhealthy individuals at high-risk were analysed with Mann Whitney Test. The confidence level is p &lt;0.05. The mean Neopterin levelsin patients with active pulmonary tuberculosis was 5.17±4.64 nmol/L, the mean Neopterin levels in group of healthy individuals athigh risk was 3.97±1.79 nmol/L. Statistical analysis by the independent samples t-test found no significant differences between groupsin Neopterin serum levels of patients with active pulmonary tuberculosis and healthy individuals at high risk (p=0.357). The meanserum levels of H2O2 of group of patients with active pulmonary tuberculosis was 26.38±3.00 μM, the mean levels of H2O2of group ofhealthy individuals at high risk of 20.69±4.46 μM. Statistical analysis with non-parametric Mann-Whitney Test was found significantdifference in the peroxide (H2O2) levels between groups of patients with active pulmonary tuberculosis and group of healthy individualat high-risk (p=0.000). The levels of Neopterin in patients with active pulmonary tuberculosis was not significantly higher comparedto the healthy individuals of high risk. Levels of peroxide (H2O2) serum in patients with active pulmonary tuberculosis was significantlyhigher compared to the group of healthy individuals at high risk. This shows that there is increased activity of macrophages in patientswith active pulmonary tuberculosis, but not effective in eliminating of Mycobacterium tuberculosis.

Serum Neopterin Level in Children with Juvenile Idiopathic Arthritis

Background: Juvenile idiopathic arthritis (JIA) is generally considered a clinical syndrome involving several disease subsets, with a number of inflammatory flows, leading to an eventual common pathway in which persistent synovial inflammation and associated damage to articular cartilage and underlying bone are present. Neoptrin is a reliable marker in the assessment of the rate of IFN-γ production. Levels of neoptrin increase in direct proportion with the level of interferon. Measurement of neopterin level is useful because of its relative stability also it is a prognostic indicator for cell-mediated immunity. Aims: This study aims to assess serum level of neopterin in patients with Juvenile Idiopathic Arthritis (JIA) in relation to the disease activity, severity and response to conventional and biological therapy. Methodology: The study was conducted on 30 patients (Group A) previously diagnosed as SoJIA, they were divided into two subgroups according to their therapy into Group AI on biological therapy (15 patients) and Group AII on conventional therapy (15 patients). These in addition to 20 healthy controls (Group B). Results: Basic clinical evaluation and laboratory investigations were done. We found that JIA patients had significantly higher levels of serum neopterin than healthy controls. We also found a highly significant difference between neopterin levels in the activity and remission states among all patients (Group AI and Group AII). Conclusion: We concluded that serum neopterin is a useful marker for cellular immune activation and also indicative of the activity of JIA. Our findings are supported by positive correlations between serum neopterin levels and other markers of activity as TLC, PLT counts, ESR, and CRP. We also concluded that serum neopterin is a sensitive and accurate predictor of disease activity where sensitivity of that test was 93.3% and accuracy was 72.5%. Recommendations: Investigating the serum neopterin measurement in other autoimmune collagen diseases. Assessment the influence of biological therapy on neopterin levels in relation to disease progression.

Neopterin and Cardiovascular Events Following Coronary Stent Implantation in Patients with Stable Angina Pectoris.

Aim: Neopterin is an activation marker for monocytes/macrophages. We prospectively investigated the predictive value of plasma neopterin levels on 2-year and long-term cardiovascular events in patients with stable angina pectoris (SAP) undergoing coronary stent implantation.Methods: We studied 123 consecutive patients with SAP who underwent primary coronary stenting (44 patients with bare metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma neopterin levels were measured on admission using HPLC. Moreover, one frozen coronary artery specimen after DES and three frozen coronary specimens after BMS were obtained by autopsy or endarterectomy, followed by immunohistochemical staining for neopterin.Results: Plasma neopterin levels were significantly higher in patients with cardiovascular events than in those without them (P < 0.001). In subgroup analyses, higher levels of plasma neopterin in patients with cardiovascular events (P < 0.001) and a positive correlation between neopterin levels and late lumen loss after stenting (P = 0.008) were observed in the BMS group but not in the DES group (P = 0.53 and P = 0.17, respectively). In long-term cardiovascular events, multivariate Cox regression analysis identified the significance of the high-neopterin group as independent determinants of cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283–3.857; P = 0.004). Immunohistochemical staining showed abundant neopterin-positive macrophages in the neointima after BMS implantation but no neopterin-positive macrophages in the neointima after DES implantation.Conclusion: These findings suggest that neopterin is associated with cardiovascular events after coronary stent implantation in patients with SAP. However, there might be a strong association between neopterin and cardiovascular events after BMS but not after DES in these patients.

Neopterin as a marker of cellular immunological response

Neopterin is a pyrazino-pyrimidine compound that belongs to the pteridine group. It is known to be a biochemical marker associated with cell-mediated immunity. It is produced by human monocytes/macrophages and dendritic cells from guanosine triphosphate (GTP) upon stimulation with interferon gamma (IFNγ), which is released by activated limphocytes Th. Neopterin is a very important clinic parameter, though the physiological role has not been exactly definited thus far. The level of neopterin reflects the stage of activation of the cellular immune system, which is important in the pathogenesis and progression of various diseases. Measuring its concentration in body fluids is used in many different areas of modern medicine, such as infectious disease, gastroenterology, transplantology and transfusiology, rheumatology or oncology. In neurological, cardio-vascular and autoimmune diseases, cell-mediated immunity is also activated, which is proved by the elevated level of this marker. Measurements of neopterin concentrations are also helpful in monitoring the therapy of patients infected with the HIV virus or treated by using immunomudulating therapy. As a result of measuring levels of neopterin in patients with neoplasms of digestive tract, increased concentration was proved, but it is not routinely used in everyday clinic practice.

Angiotensin type 1 receptor A1166C polymorphism and systemic lupus erythematosus: correlation with cellular immunity and oxidative stress markers.

Angiotensin II, one of the rennin-angiotensin system components, is important in the cardiovascular hemodynamic and plays an important role in the development of cardiovascular disease in systemic lupus erythematosus (SLE) patients. The angiotensin II, through interaction with angiotensin II type 1 receptor (AGTR1), promotes proliferation, inflammation and fibrosis. The single nucleotide polymorphism of the AGTR1 (dbSNP: rs5186) gene can be associated with development and progression of SLE disease. The aims of this study were to compare the frequency of AGTR1 rs5186 in SLE patients with healthy individuals and to evaluate possible association between AGTR1 A1166C gene polymorphism and serum level of lipids, neopterin and malondialdehyde in SLE patients from a population of West Iran. One hundred SLE patients and 98 healthy subjects were studied. The AGTR1 A1166C polymorphism was detected by polymerase chain reaction- restriction fragment length polymorphism method and the serum lipid profile was obtained by enzymatic method. Neopterin and malondialdehyde were detected using high-performance liquid chromatography. We did not detect significant association between AGTR1 A1166C polymorphism and the risk of SLE. The levels of triglyceride (225 ± 118 mg/dl), neopterin (30 ± 24 nmol/l) and malondialdehyde (25 ± 9.6 nmol/l) in SLE patients were significantly higher than those in control subjects (139 ± 56 mg/dl, p = 0.03, 6.4 ± 2, p = 0.03, 9.4 ± 2.5 nmol/l, p = 0.01, respectively). Individuals with AGTR1 AC + CC genotype had higher levels of total cholesterol and malondialdehyde compared with those with AGTR1 AA genotype. SLE patients with either AGTR1 AA or AGTR1AC + CC genotype had significantly higher malondialdehyde or neopterin levels compared with the corresponding control subjects. In conclusion, although the present study did not find any association between AGTR1 A1166C polymorphism and the risk of SLE, the presence of this polymorphism was associated with higher levels of malondialdehyde and higher concentration of neopterin in patients.