Higher Neopterin Levels Research Articles

Neopterin is Associated with Disease Severity and Outcome in Patients with Non-Ischaemic Heart Failure.

Inflammation and immune activation play an important role in the pathogenesis of cardiac remodelling in patients with heart failure. The aim of this study was to assess whether biomarkers of inflammation and immune activation are linked to disease severity and the prognosis of heart failure patients. In 149 patients (65.8% men, median age 49.7 years) with heart failure from nonischaemic cardiomyopathy, the biomarkers neopterin and C-reactive protein were tested at the time of diagnosis. Patients were followed-up for a median of 58 months. During follow-up, nineteen patients died, five had a heart transplantation, two needed a ventricular assistance device, and twenty-one patients had to be hospitalised because of heart failure decompensation. Neopterin concentrations correlated with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations (rs = 0.399, p < 0.001) and rose with higher New York Heart Association (NYHA) class (I: 5.60 nmol/L, II: 6.90 nmol/L, III/IV: 7.80 nmol/L, p = 0.033). Higher neopterin levels were predictive for an adverse outcome (death or hospitalisation due to HF decompensation), independently of age and sex and of established predictors in heart failure such as NYHA class, NT-proBNP, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LV-EF) (HR 2.770; 95% CI 1.419–5.407; p = 0.003). Patients with a neopterin/eGFR ratio ≥ 0.133 (as a combined marker for immune activation and kidney function) had a more than eightfold increased risk of reaching an endpoint compared to patients with a neopterin/eGFR ratio ≤0.065 (HR 8.380; 95% CI 2.889–24.308; p < 0.001). Neopterin is associated with disease severity and is an independent predictor of prognosis in patients with heart failure.

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

The role of neopterin and anti-Mullerian hormone in unexplained recurrent pregnancy loss – a case-control study

This case-control study was conducted to assess whether neopterin (NP) and anti-Mullerian hormone (AMH) can be used as markers in the condition of unexplained recurrent pregnancy loss (RPL). To the best of our knowledge, this is the first work which has studied the association between AMH, NP and RPL. A total of 110 patients were included; 53 women who had at least two consecutive unexplained miscarriages (<12 weeks) made up the study group. The control group was established from 57 women who never had a miscarriage and had at least one healthy birth history. Peripheral blood samples were collected from each patient to analyse the AMH and NP concentrations. The results suggested that mean level of AMH (1.38 ± 0.683 ng/ml) in the patient’s group was significantly lower than the control group (1.84 ± 0.718 ng/ml). The mean levels of NP were significantly higher in the patient group (1.69 ± 0.486 vs. 1.38 ± 0.431 ng/ml).IMPACT STATEMENTWhat is already known about this subject? To the best of our knowledge, no previous studies about the association among AMH, NP and RPL were found in the literature.What do the results of this study add? This pioneer study demonstrates the significant relationship between the unexplained RPL with the increased levels of NP and decreased AMH.What are the implications of these findings for clinical practice and/or further research? NP and AMH may play an effective role in illuminating the condition of unexplained RPL. High levels of NP and low values of AMH in patients with RPL can be used as predictive markers for this clinical situation. If the causes of high levels of NP and low levels of AMH can be better illuminated, new treatments towards these causes can be developed to help such patients become childbearing.

SYPHILIS;

Objectives: To assess serum Neopterin levels in blood donors of local population and to study its relationship with transfusion transmitted infections (TTIs) including syphilis. Study Design: Descriptive cross-sectional study. Place and Duration of Study: This study was carried out in the Department of Physiology LNMC in collaboration with Basic Medical Sciences Institute, (BMSI), and Jinnah Post Graduate Medical Centre (J.P.M.C.) Karachi, from Jan to July 2015.”Methods: Total 174 blood donors were included in the study through random sampling technique. They were screen through the standard procedures used for screening at the JPMC blood bank for WHO recommended diseases. Neopterin was estimated using ELISA. Data analysis was performed using SPSS version 21. Chi square and ANOVA were applied at a confidence level of 95%.”Results: Neopterin level in the sera of syphilis positive blood donors was 5.86 ± 0.78 nmol/l which was within normal range below the cutoff value of 10 nmol/l. Neopterin content in the serum of blood donors who were negative for transfusion transmitted infections was 6.23± 2.19 nmol/l as compared to blood donors testing positive for transfusion transmitted viral infections showing high Neopterin level of 15.10 ± 4.93 nmol/l. (P value 0.001).”Conclusion: Neopterin levels were found to be within normal limits in blood donors testing positive for syphilis However in blood donors with transfusion transmitted viral infections serum neopterin levels were elevated.

Can neopterin be a useful immune biomarker for differentiating gastric intestinal metaplasia and gastric atrophy from non-atrophic non-metaplastic chronic gastritis?

IntroductionHelicobacter pylori (H. pylori) is closely related to pre-neoplastic lesions such as gastric atrophy (GA), gastric intestinal metaplasia (GIM) and eventually gastric cancer (GC). The diagnosis of GIM and GA is usually based on endoscopic and histopathological features. Nowadays, there are no recognized good serological markers of GIM and GA. Neopterin is an important marker of cellular inflammation. In this study, we aimed to comparatively evaluate C-reactive protein (CRP) and neopterin levels in patients with GIM, GA and chronic gastritis, and to show the increased serum neopterin levels in GIM and GA according to non-atrophic and non-metaplastic chronic gastritis. Patients and methods98 patients with GIM and 68 patients with GA and 70 patients with non-atrophic non-metaplastic gastritis were included in the study. CRP and neopterin levels were assessed in patients and controls. ResultsCRP and neopterin levels were significantly higher in patients with GIM and GA than in controls (p<0.05 and p<0.001, respectively). A multiple logistic regression analysis showed that high levels of serum neopterin were positively correlated with GIM and GA. According to the ROC curve analysis, the best cut-off value to differentiate between patients with GIM and/or GA from controls was ≥10.15nmol/l (p<0.001) for serum neopterin levels and ≥1.95mg/l (p<0.001) for serum CRP levels. DiscussionCRP and neopterin levels are significantly increased in GIM and GA. Neopterin may be a useful biomarker and diagnostic test for detecting GIM and GA in clinical practice. CRP levels may be helpful for this observation.

High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infections

BackgroundThe host response to intruders in the central nervous system (CNS) may be beneficial but could also be harmful and responsible for neurologic symptoms and sequelae in CNS infections. This immune response induces the activation of the kynurenine pathway (KP) with the production of neuroactive metabolites. Herein, we explored cytokine and KP responses in cerebrospinal fluid (CSF) and serum in patients with encephalitis, aseptic, and bacterial meningitis.MethodsCytokines were measured in CSF and serum by multiplex assay in adult patients with encephalitis of infectious, autoimmune or unknown etiology (n = 10), aseptic meningitis (ASM, n = 25), acute bacterial meningitis (ABM, n = 6), and disease control patients with similar symptoms but without pleocytosis in CSF (n = 42). Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was used to measure KP metabolites in CSF and serum.ResultsA characteristic pattern of increasing cytokine levels and KP metabolites was found in CSF from encephalitis to ASM, with the highest levels in ABM. In ASM and ABM, most inflammatory mediators, including IL-6, IL-8, and IFN-inducible protein-10 (IP-10), showed markedly elevated levels in CSF compared with serum, indicating production within the CNS. In contrast to most mediators, the highest level of IP-10 was found in the ASM group, suggesting a potential role for IP-10 in aseptic/viral meningitis. Neopterin and IP-10 were associated with marked changes in KP metabolites in CSF with increasing kynurenine/tryptophan ratio reflecting indoleamine 2,3-dioxygenase activity. Neopterin, a marker of IFN-γ activity, was associated with an unfavorable balance between neuroprotective and neurotoxic tryptophan metabolites.ConclusionWe show that parenchymal and meningeal inflammations in CNS share a characteristic cytokine profile with a general immune response in the CSF with limited influence from the systemic circulation. IFN-γ activity, assessed by neopterin and IP-10 levels, may play a role in the activation of the KP pathway in these patients, potentially mediating neurotoxic effects.

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.

Neopterin is associated with hippocampal subfield volumes and cognition in HIV

ObjectiveHIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults.MethodsCross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1β, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined.ResultsNo inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition.ConclusionImmune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

Role of neopterin as a biochemical marker for peripheral neuropathy in pediatric patients with type 1 diabetes: Relation to nerve conduction studies

BackgroundNeopterin, a marker of inflammation and cellular immune response, is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (DPN) is associated with inflammatory/immune processes and therefore, we hypothesized that neopterin could be used as a marker of neuropathy in type 1 diabetes mellitus (T1DM). AimTo measure neopterin levels in children and adolescents with T1DM and assess its possible relation to DPN and nerve conduction studies (NCS). MethodsSixty patients aged ≤18 years and >5 years disease duration were subjected to neurological assessment by neuropathy disability score (NDS) and NCS for median, ulnar, posterior tibial and common peroneal nerves. Mean fasting blood glucose, lipid profile, HbA1c, high sensitivity C-reactive protein (hs-CRP) and serum neopterin levels were assessed. Patients were compared with 30 age- and sex-matched healthy controls. ResultsThe frequency of DPN according to NDS was 40 (66.7%) patients out of 60 while NCS confirmed that only 30 of those 40 patients had this complication (i.e. 50% out of the total studied patients). Neopterin levels were significantly higher in patients with DPN than those without (median [IQR], 53.5 [35–60] nmol/L versus 17 [13−32] nmol/L) and healthy controls (5.0 [3.2–7.0] nmol/L) (p < 0.001). Significant positive correlations were found between neopterin levels and HbA1c (r = 0.560, p = 0.005), serum creatinine (r = 0.376, p = 0.003), total cholesterol (r = 0.405, p = 0.026) and hs-CRP (r = 0.425, p = 0.012) among patients with DPN. Neopterin levels were positively correlated to motor latency of tibial and common peroneal nerves as well as motor and sensory latencies of median and ulnar nerves. Logistic regression analysis revealed that neopterin was a significant independent variable related to DPN (Odds ratio, 2.976). Neopterin cutoff value 32 nmol/L could differentiate patients with and without DPN with 100% sensitivity and 96.7% specificity. ConclusionsNeopterin could be used as an early reliable serum biomarker for DPN in pediatric patients with T1DM.

185 (PB-086) - 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.

Neopterin, kynurenine and tryptophan as new biomarkers for early detection of rectal anastomotic leakage.

IntroductionAt present, there are no strong predictors, nor a useful scoring system, that clearly identifies patients at risk for anastomotic leakage.AimThis study aimed to investigate a new method that assesses this risk by monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids.Material and methodsThis prospective study included patients who underwent elective rectal resection for carcinoma. The basic condition for inclusion was rectal anastomosis using the double-stapling technique. Preoperative levels of neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and urine samples. These levels were then monitored for 6 postoperative days in venous blood, urine, and abdominal drainage fluid.ResultsA total of 42 patients were enrolled in the study. Thirty-six patients underwent a laparoscopic resection and 6 patients had an open procedure. No differences were found among neopterin, tryptophan, and kynurenine serum levels. However, the groups were observed to have significant differences in the urinary neopterin/creatinine ratio: the preoperative neopterin/creatinine ratio was 139.5 μmol/mol in the group with leakage, vs 114.8 μmol/mol in the group without complications, p = 0.037. The same results were observed during the postoperative period, p = 0.012. Additionally, the group with complications had a higher mean value of neopterin in drainage fluid, p = 0.048.ConclusionsOur study demonstrated that high preoperative levels of urinary neopterin could be interpreted as a risk for anastomotic leakage. Moreover, pathological levels of neopterin in urine and abdominal drainage fluid could be useful for early identification of anastomotic leakage during the postoperative period prior to its clinical development.

Content of α-, -interferon and neopterin in blood serum of women with parvovirus infection in different periods of pregnancy

The aim of the study was to determine α-, g-interferon (IFN) and neopterin levels in blood serum of pregnant women with a parvovirus infection.Methods and materials: There were examined 129 pregnant women, infected with a parvovirus В19, and 16 women with physiological pregnancy in I, II and III trimesters. Each group of pregnant women (I, II, III) was divided in two subgroups, depending on the presence or absence of clinical complications. The quantitative evaluation of α-, g-IFN and neopterin content in blood serum was realized by the method of immune-enzyme analysis. Results of research: Blood serum of infected pregnant women contained increased α-and g-IFN levels, most expressed at studying IFN-γ levels that reliably exceeded control indices in I-III groups in 3,4-2,9-2,1 times respectively. At the presence of clinical complications in different periods of pregnancy women demonstrated the reliably decreased α-IFN level and reliably increased g-IFN level compared with pregnant women without clinical complications. High levels of neopterin were revealed in blood serum of infected women that testifies to the activation of a monocytic link of the cellular immunity at the impact of g-IFN. At comparing the subgroups of pregnant women it was established, that changes of the neopterin level in blood serum relative to control values had the unidirectional character, but women with clinical complications of pregnancy demonstrated the more essential exceed of control values in different trimesters– in 2,9; 2,9 and 3,1 times.Conclusions. The increase of IFN-g and neopterin up to high values reflects the activation of a cellular immunity link and can play an important role in the pathogenesis of pregnancy complications

Neopterin levels and systemic inflammatory response syndrome in pediatric critically ill patients

Abstract Introduction Neopterin and biopterin are subproducts of redox reactions, which act as cofactor of enzymes responsible for nitric oxide production. We hypothesized that plasma neopterin suffers different evolution during the first days of a critically ill child. Methods Single-center prospective observational study in patients 7 days to 14 years admitted to our PICU and that met SIRS criteria. Neopterin and biopterin levels as well as other acute phase reactants were collected at admission and at 24 h. Results A total of 28 patients were included, 78.9% male, median age 5.04 years (interquartile range [IQR] 1.47–10.26), PRISM II 2.0% (IQR 1.1–5.0). Mechanical ventilation (MV) in 90% of patients, median duration of 6.0 h (IQR 3.7–102.0); median PICU length of stay 5.0 days (IQR 2.7–18.7), maximum VIS through 0 (IQR 0–14). Baseline neopterin level 2.3 ± 1.2 nmol/l and at 24 h 2.3 ± 1.4 nmol/l. Baseline biopterin is 1.3 ± 0.5 nmol/l and 1.4 ± 0.4 nmol/l at 24 h. Neopterin levels significantly higher in patients with PICU length of stay >6 days (p = .02), patients who needed MV >24 h (p = .023) and those who developed complications (p = .05). Neopterin correlates directly and statistically significant with the duration of MV (rho = .6, p = .011), PICU length of stay (rho = .75, p Discussion There is a higher neopterin level when longer PICU stay, higher VIS score, longer MV and occurrence of complications, pointing at the involvement of an activation of the cellular immune system.

Neopterin levels and systemic inflammatory response syndrome in pediatric critically ill patients

Neopterin and biopterin are sub-products of redox reactions, which act as cofactors of enzymes responsible for nitric oxide production. The hypothesis is presented that plasma neopterin and biopterin evolve differently during the first days in a critically ill child. A single-centre prospective observational study was conducted on patients 7 days to 14 years admitted to our Paediatric Intensive Care Unit (PICU) and that met Systemic inflammatory response syndrome (SIRS) criteria. Neopterin and biopterin levels, as well as other acute phase reactants, were collected at admission and at 24 h. A total of 28 patients were included, of which 78.9% were male, The median age was 5.04 years (interquartile range [IQR] 1.47-10.26), and PRISM II 2.0% (IQR 1.1-5.0). Mechanical ventilation (MV) was used in 90% of patients, with a median duration of 6.0 hrs (IQR 3.7-102.0). The median length of stay in PICU was 5.0 days (IQR 2.7-18.7), maximum VIS mean of 0 (IQR 0-14). Baseline neopterin level was 2.3±1.2 nmol/l and at 24 h it was 2.3±1.4 nmol/l. Baseline biopterin was 1.3±0.5 nmol/l and 1.4±0.4 nmol/l at 24 h. Neopterin levels were significantly higher in patients with PICU length of stay > 6 days (P=.02), patients who needed MV >24 h (P=.023), and those who developed complications (P=.05). Neopterin correlates directly and is statistically significant with the duration of MV (rho=.6, P=.011), PICU length of stay (rho=.75, P<.0001), and VIS (rho=.73, P=.001). Additionally, biopterin directly correlates with the PRISM (rho=.61, P=.008). There is a higher neopterin level when there is a longer PICU stay, higher VIS score, longer time on MV, and occurrence of complications, indicating the involvement of an activation of the cellular immune system.

Serum neopterin concentrations and tryptophan degradation pattern in patients with late stage larynx carcinoma

AbstractAs the disease-free 5-year-survival of late stage laryngeal carcinoma patients is extremely low, indoleamine-2,3-dioxygenase-1 (IDO)-induced tryptophan degradation may represent an immune escape mechanism which plays an important role in cancer spreading in advanced stage laryngeal cancers. We examined whether the late stage laryngeal cancer enhances tumor immune evasion by the expression of systemic IDO activities and chronic cellular immune activation. Twenty-two of 42 male laryngeal cancer patients were classified as late stage cancer according to American Joint Committee on Cancer (AJCC) criteria. Their serum neopterin, tryptophan and kynurenine concentrations were compared with 30 cancer-free individuals. IDO activity was approved by correlation between serum neopterin and kynurenine/tryptophan. Late stage cancer patients preoperatively showed a significantly higher IDO activity compared to controls and early stage cancer cases. Six months after tumor removal, late stage cancer patients although having higher serum neopterin concentration compared to early stage patients or controls, they showed a significant decrease in IDO activity and tryptophan consumption. Increased systemic IDO activity may provoke the escape of tumor cells from the immune surveillance of the host. High IDO activity is due to the presence of tumor mass. Persistence of high serum neopterin levels despite tumor removal may indicate poor prognosis.

Diagnostic and Prognostic Value of Inflammatory Parameters Including Neopterin in the Setting of Pneumonia, COPD, and Acute Exacerbations

ABSTRACTAcute exacerbations and community-acquired pneumonia (CAP) are severe complications in patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed inflammatory parameters in serum including C-reactive protein (CRP), procalcitonin (PCT), and serum neopterin (NPT) to determine their potential to differentiate between patients with CAP+COPD and with acute exacerbations of COPD (AECOPD) without pneumonia. 102 (39 women and 63 men) patients were included in this retrospective study, of whom 48 presented with CAP without underlying COPD, 20 with CAP+COPD and 34 with AECOPD. CRP, PCT, and blood counts were determined by routine automated tests, and NPT concentrations were determined by ELISA. The ratios of CRP to NPT levels were calculated. Upon patient admission, CRP, PCT, and NPT levels were significantly higher in patients with CAP compared to those in AECOPD patients. CRP/NPT ratio was lower in AECOPD compared to CAP (+/−COPD) patients. Positive correlations were found between duration of hospitalization and CRP levels and the CRP/NPT ratio at study entry. Patients who were readmitted within 30 days tended to have higher NPT levels at initial presentation. Patients under ongoing corticosteroid treatment presented with lower inflammatory parameters. The CRP/NPT-ratio was suited well to discriminate between AECOPD and CAP on the basis of COPD, a CRP/NPT cutoff of 0.346 provided a sensitivity of 65% and a specificity of 79%. The combinatory use of inflammatory patterns might help to differentiate patients with AECOPD from those with CAP on the basis of COPD.

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy.

QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas.

Cerebrospinal fluid levels of neopterin are elevated in delirium after hip fracture.

BackgroundThe inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium.MethodsIn this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography.ResultsSixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27.1 nmol/mL, p = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery (p = 0.02 for CSF and p = 0.03 for serum).ConclusionsThis study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes.

Maternal plasma total neopterin and kynurenine/tryptophan levels during pregnancy in relation to asthma development in the offspring

Neopterin levels and kynurenine/tryptophan ratios (KTRs) increase with IFN-γ stimulation, indicating TH1 immunity, and thus might be inversely associated with asthma. We sought to examine the association of maternal neopterin levels and KTRs during pregnancy with asthma in the offspring. We analyzed the associations of maternal plasma total neopterin levels and KTRs in midpregnancy with asthma at age 7years among 2883 children in the Norwegian Mother and Child Cohort Study. Asthma was classified either based on registered dispensed asthma medications in the Norwegian Prescription Database or maternal report. We calculated adjusted relative risks using log-binomial regression. The median gestational week of blood sampling was 18weeks (interquartile range, 17-19weeks). The risk of dispensed asthma medications at age 7years was highest among children of mothers in the highest quartile of neopterin levels, whereas the risk was similar in the 3 lowest quartiles. The adjusted relative risk of dispensed asthma medications was 1.66 (95% CI, 1.16-2.38) when comparing children of mothers in the highest quartile with those in the 3 lowest quartiles. Asimilar association was observed for maternal report of asthma at age 7years. When we evaluated allergic versus nonallergic asthma, neopterin levels tended to be associated with nonallergic asthma. Maternal KTR was not associated with asthma development. Our findings indicate that high maternal levels of neopterin, a marker of cellular immune activation, during pregnancy were positively associated with asthma in offspring. Experimental studies would be needed to further elucidate underlying mechanisms.

The role of Neopterin in cardiovascular disease

Inflammation plays a key role in the initiation and progression of atherosclerosis but also in the pathophysiology of atheromatous plaque disruption and the development of acute coronary syndromes. Neopterin is a marker of inflammation and of immune system activation, it is synthesized by macrophages, that, once activated, release this substance. Indeed, in clinical evaluation of patients, measurements of plasma levels of neopterin are usually used to evaluate progression of viral infections, renal transplant rejection, severe systemic inflammatory diseases, nephritic syndrome and several autoimmune diseases. This mediator is able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Recent data indicate that serum levels of neopterin are elevated in patients with coronary and peripheral artery disease and seem to be a prognostic marker for major adverse cardiovascular events. In particular, neopterin levels predict future major cardiac and vascular adverse events in patients presenting with chronic coronary artery disease, with acute coronary syndromes, and in those with critical limb ischemia. This renders this molecule a useful marker of atherosclerotic plaque activity, permitting the identification of the subjects at highest risk for major adverse cardiovascular events. In line with the above mentioned evidences, patients with high neopterin levels may require aggressive risk factor modification and intensive medical treatment irrespective of the severity of their coronary artery disease. This data suggest a potential clinical use of neopterin as a marker for disease activity in patients with cardiovascular disease.