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Dietmar Fuchs - One of the best experts on this subject based on the ideXlab platform.
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Heritability of plasma Neopterin levels in the Old Order Amish.
Journal of neuroimmunology, 2017Co-Authors: Uttam K. Raheja, Dietmar Fuchs, Christopher A. Lowry, Sarah H. Stephens, Mary Pavlovich, Hira Mohyuddin, Hassaan Yousufi, Kathleen A. Ryan, Jeffrey R. O'connell, Lisa A. BrennerAbstract:Abstract Background We examined the heritability of Neopterin, a biomarker for cell-mediated immunity and oxidative stress, and potentially for psychiatric disorders, in the Old Order Amish. Methods Plasma Neopterin levels were determined in 2015 Old Order Amish adults. Quantitative genetic procedures were used to estimate heritability of Neopterin. Results Heritability of log-Neopterin was estimated at 0.07 after adjusting for age, gender, and household ( p = 0.03). The shared household effect was 0.06 ( p Conclusions We found a low heritability of Neopterin and small household effect, suggesting that non-household environmental factors are more important determinants of variance of Neopterin levels in the Amish.
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cerebrospinal fluid Neopterin is brain derived and not associated with blood csf barrier dysfunction in non inflammatory affective and schizophrenic spectrum disorders
Journal of Psychiatric Research, 2013Co-Authors: Leonie K Kuehne, Hansotto Reiber, Karl Bechter, Lars Hagberg, Dietmar FuchsAbstract:Many psychiatric patients have a minor blood-CSF barrier dysfunction and increased Cerebrospinal fluid (CSF) Neopterin concentrations. The source of normal CSF Neopterin, a biomarker in inflammatory and non-inflammatory neurological diseases, has never been shown explicitly, a precondition for sensitive detection of pathologically increased CSF Neopterin. Neopterin concentrations (ELISA) in CSF and serum of normal controls (n = 26) are evaluated by inter-individual variation propagation. Normal CSF Neopterin is brain-derived: The inter-individual variation of CSF Neopterin in the control group does not depend on serum Neopterin concentration variation (coefficient of variation, CV-CSF = 9.7% < CV-serum = 24.5%). Additionally individual normal CSF Neopterin concentrations are invariant to the variation of the albumin quotient, QAlb, i.e. CSF Neopterin does not derive from leptomeninges. Subsequently CSF Neopterin was interpreted with reference to its absolute concentration in CSF (cut off = 5.5 nmol/l). Patients (N = 44), retrospectively selected from a larger group with schizophrenic and affective spectrum disorder, are characterized by the absence of any clinical and neurochemical signs of inflammation. In this group 30% had an increased CSF Neopterin concentration and 30% had an increased QAlb with only 7% combined pathologies. Increased CSF Neopterin did not correlate with the blood-CSF barrier dysfunction. In the discussion we point to possible sources of both independent pathologies, connected either with reduced CSF flow rate (QAlb) or microglial activation (Neopterin). With CSF Neopterin analysis earlier in vitro studies about microglia activation in schizophrenic spectrum disorders or corresponding therapeutic efforts could get a more direct, in-vivo analytical tool.
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cerebrospinal fluid Neopterin decay characteristics after initiation of antiretroviral therapy
Journal of Neuroinflammation, 2013Co-Authors: Aylin Yilmaz, Dietmar Fuchs, Lars Hagberg, Constantin T Yiannoutsos, Richard W Price, Kathryn Crozier, Serena Spudich, Magnus GisslenAbstract:Background: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of Neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF Neopterin after ART-mediated viral suppression. Methods: CSF and blood Neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naive or had been off ART for ≥ 6 months. We used a non-linear model to estimate Neopterin decay in response to ART and a stable Neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results: Non-HAD patients were followed for a median 84.7 months. Though CSF Neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF Neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF Neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF Neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions: After virologically suppressive ART, abnormal CSF Neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.
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Neopterin as a predictor of total and cardiovascular mortality in individuals undergoing angiography in the ludwigshafen risk and cardiovascular health study
Clinical Chemistry, 2009Co-Authors: Dietmar Fuchs, Tanja B Grammer, Bernhard O Boehm, Bernhard R Winkelmann, Winfried MaerzAbstract:Background: Neopterin is produced upon activation of the cell-mediated immune response, and may be a novel risk marker for adverse outcomes resulting from coronary artery disease. Methods: We measured Neopterin in 1801 study participants with and 511 without angiographic coronary artery disease. Rates of death were determined after a median follow-up of 8.0 years. Results: Estimated glomerular filtration rate and N-terminal pro-B–type natriuretic peptide (NT-proBNP) were the strongest predictors of Neopterin. Neopterin was positively related to age and inversely related to LDL cholesterol, HDL cholesterol, and triglycerides. Use of lipid-lowering drugs lowered Neopterin. Sex, body mass index, diabetes mellitus, hypertension, smoking status, Friesinger coronary score, and clinical instability at presentation were not associated with Neopterin. Unlike C-reactive protein, Neopterin was not increased in unstable angina pectoris, non–ST–elevation myocardial infarction, or ST-elevation myocardial infarction. In the third and fourth quartiles of Neopterin, unadjusted hazard ratios for death from any cause were 1.94 (95% CI 1.44–2.61) and 3.32 (95% CI 2.53–4.30) compared to individuals in the first quartile, whereas hazard ratios for death from cardiovascular causes were 2.14 (95% CI 1.44–3.18) and 3.84 (95% CI 2.67–5.52), respectively. Neopterin remained predictive of total and cardiovascular mortality after adjusting for sex, age, body mass index, type 2 diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol, triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical status at presentation, but NT-proBNP substantially weakened this association. Conclusions: Neopterin is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease.
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Association between Neopterin in cord blood, urinary Neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 2006Co-Authors: Elisabeth Horak, Christian Murr, Werner Streif, Katharina Schroecksnadel, Harald Schennach, Dietmar FuchsAbstract:It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of Neopterin. Thus, the determination of Neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether Neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary Neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood Neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary Neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary Neopterin concentrations at age 6 yr, and between cord blood Neopterin and later atopic disease. Urinary Neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood Neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary Neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.
Bohuslav Melichar - One of the best experts on this subject based on the ideXlab platform.
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Neopterin as a biomarker of immune response in cancer patients.
Annals of translational medicine, 2017Co-Authors: Bohuslav Melichar, Lenka Kujovská Krčmová, Marie Bartouskova, Martina Spisarová, Lenka Javorska, Hana ŠtudentováAbstract:With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine. Increased urinary or serum concentrations of Neopterin have been associated with poor prognosis across a spectrum of malignant disorders of different primary location. Neopterin concentration in peripheral blood as well as in the tumor microenvironment correlates with phenotypic and functional changes of lymphocytes, indicating immune dysfunction. Increased Neopterin concentrations are also accompanied by increased rate of conversion of tryptophan to kynurenine. Increasing Neopterin concentrations also accompany side effects of anticancer treatment and could predict subsequent complications. Although almost four decades have elapsed since the discovery of increased Neopterin concentrations in cancer patients, the full potential of Neopterin as a biomarker in this setting has not been so far realized.
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Urinary Neopterin concentrations during radiotherapy for gynecological cancer
Pteridines, 2014Co-Authors: Sachin Vipin Trivedi, Bohuslav Melichar, Hana Študentová, Hana Kalábová, Lenka Kujovská Krčmová, Dagmar Solichová, Pavel Veselý, Martin Majirský, Martin DoleželAbstract:AbstractNeopterin is a biomarker of host response to neoplasia. In the present study, urinary Neopterin was determined during the course of (chemo)radiation in ten patients with gynecological tumors (nine patients with cervical carcinoma and one patient with carcinoma of the vulva). Baseline urinary Neopterin concentrations were, generally, above the normal range. Neopterin concentrations were relatively stable during the first 5 weeks of combined (chemo)radiation. Marked peaks of Neopterin concentrations reflected the emergence of complications. Neopterin could represent a useful biomarker for the assessment of the condition of the patients during this aggressive therapy.
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Prognostic Significance of Serum Neopterin in Patients with Esophageal Carcinoma
Pteridines, 2012Co-Authors: Jan Cincibuch, Eva Malirova, Karel Cwiertka, Hana Procházková-Študentová, Michaela Zezulová, Čestmír Neoral, Hana Kalábová, Lenka Kujovská Krčmová, Dagmar Solichová, Bohuslav MelicharAbstract:Abstract Increased concentrations of Neopterin have been described in patients with tumors of different primary locations, but reports on Neopterin in patients with carcinoma of the esophagus are still very limited. We have studied serum Neopterin in 45 patients with histologically verified carcinoma of the esophagus. Serum Neopterin was determined with radioimmunoassay. Neopterin concentrations above median (6.5 nmol/L) were associated with inferior prognosis in patients with early esophageal carcinoma. In multivariate analysis, tumor stage and serum Neopterin were predictors of survival in patients without distant metastases. In conclusion, serum Neopterin is an independent prognostic factor in patients with esophageal carcinoma.
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Serum Neopterin in Patients with Malignant Melanoma
Pteridines, 2009Co-Authors: Petr Beneš, Bohuslav Melichar, Hana Študentová, Miloslava Kapustová, Eva Malirova, Petr Schneiderka, Vlastislav Šrámek, Karel CwiertkaAbstract:Abstract Increased serum or urinary concentrations of Neopterin have been described in patients with tumors of different primary locations, but reports on Neopterin in patients with melanoma are scanty. We have studied serum Neopterin and a melanoma marker, S-100-beta, in 41 patients with melanoma. Serum Neopterin and S-100-beta were determined by immunoassay. Neopterin concentrations were significantly increased compared to controls only in patients with active disease, but not in patients without evidence of disease activity. Serum Neopterin and S-100-beta in patients with active disease were higher than in patients without evidence of disease activity. In patients a significant correlation existed between Neopterin and S-100-beta (rs = 0.33, p <0.05), and, in patients without active disease, there was also a correlation between Neopterin and age (rs = 0.51, p <0.01). In conclusion, increased serum Neopterin in patients reflects disease activity. A significant correlation was observed between serum Neopterin and S-100-beta. Future studies are necessary to demonstrate whether the combined measurement of serum Neopterin and S-100-beta could be useful in the detection of recurrence in patients with melanoma.
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Serum Neopterin, Retinol and Alpha-tocopherol in Patients with the Carcinoma of the Esophagus
Pteridines, 2009Co-Authors: Jan Cincibuch, Bohuslav Melichar, Hana Študentová, Miloslava Kapustová, Eva Malirova, Petr Schneiderka, Lenka Kujovská Krčmová, Dagmar Solichová, Kasparová M, Jarmila JuránováAbstract:Increased serum or urinary concentrations of Neopterin have been described in patients with tumors of different primary locations, but reports on Neopterin in patients with esophageal carcinoma are scanty. We have studied serum Neopterin, retinol and alpha-tocopherol in 45 patients with carcinoma of the esophagus or gastroesophageal junction. Serum Neopterin was determined using radioimmunoassay. Retinol and alpha-tocopherol were deter- mined by high-performance liquid chromatography. Serum Neopterin in patients with carcinoma of the esopha- gus was significantly increased while retinol and alpha-tocopherol were significantly decreased compared to con- trols. No correlation of Neopterin with hemoglobin or peripheral blood cell counts was observed. During chemoradiation, Neopterin increased significantly, while retinol and alpha-tocopherol did not change. In conclu- sion, the present study demonstrates increased serum Neopterin and decreased retinol and alpha-tocopherol con- centrations in patients with esophageal carcinoma. Chemoradiation induced a further increase of serum Neopterin concentrations.
Christian Murr - One of the best experts on this subject based on the ideXlab platform.
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Association between Neopterin in cord blood, urinary Neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 2006Co-Authors: Elisabeth Horak, Christian Murr, Werner Streif, Katharina Schroecksnadel, Harald Schennach, Dietmar FuchsAbstract:It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of Neopterin. Thus, the determination of Neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether Neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary Neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood Neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary Neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary Neopterin concentrations at age 6 yr, and between cord blood Neopterin and later atopic disease. Urinary Neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood Neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary Neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.
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Neopterin as a Marker for Immune System Activation
Current drug metabolism, 2002Co-Authors: Christian Murr, Barbara Wirleitner, Bernhard Widner, Dietmar FuchsAbstract:Increased amounts of Neopterin are produced by human monocytes / macrophages upon stimulation with the cytokine interferon-γ. Therefore, measurement of Neopterin concentrations in body fluids like serum, cerebrospinal fluid or urine provides information about activation of T helper cell 1 derived cellular immune activation. Increased Neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes. But also in neurological and in cardiovascular diseases cellular immune activation indicated by increased Neopterin production, is found. Major diagnostic applications of Neopterin measurements are, e.g. monitoring of allograft recipients to recognize immunological complications early. Neopterin production provides prognostic information in patients with malignant tumor diseases and in HIV-infected individuals, high levels being associated with poorer survival expectations. Neopterin measurements are also useful to monitor therapy in patients with autoimmune disorders and in individuals with HIV infection. Screening of Neopterin concentrations in blood donations allows to detect acute infections in a non-specific way and improves safety of blood transfusions. As high Neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like α-tocopherol, Neopterin can also be regarded as a marker of reactive oxygen species formed by the activated cellular immune system. Therefore, by Neopterin measurements not only the extent of cellular immune activation but also the extent of oxidative stress can be estimated.
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Helicobacter pylori infection and Neopterin
Pteridines, 2001Co-Authors: Maximilian Ledochowski, Christian Murr, Cornelia Lass-flörl, Dietmar FuchsAbstract:In order to find out whether chronic immune stimulation is associated with Helicobacter pylori infection we studied 425 healthy individuals (aged 57.6 ± 9.22 years, s.d.) who were performing a health check up without having any specific health problems. Blood was drawn for Hpylori antibody testing, determination of routine laboratory parameters, differential blood count and measuring Neopterin concentrations. In addition, in individuals seropositive for H pylori, measurement of 13C02 exhalation after administration of 75 mg 13C-Urea was performed to test for the presence of these microorganisms in the gut. One hundred and ninety subjects were H pylori seropositive (antibody titer> 4) and they had higher serum Neopterin concentrations (serum Neopterin: 6.38 nM ± 3.3 S.D.) compared to seronegative subjects (serum Neopterin: 5.74 ± 2.7 nM, p =0.027, Student's ttest). Among the H pylori seropositive individuals no such difference existed between breath test positive (serum Neopterin: 6.1 ± 3.1 nM) and negative ones (serum Neopterin: 6.1 ± 2.0 nM; p = n. s.). Increased production of Neopterin is indicative for an activated cellular immune response. Antibody seropositive patients present with higher Neopterin levels than seronegatives even when H pylori seemed to be no longer present in the gut. Surprisingly Neopterin concentrations were not related to the presence/absence of bacteria in the gut. Higher Neopterin concentrations in H pylori seropositive individuals would be in good agreement with the view of H pylori infection as a risk factor for developing atherosclerosis, since in earlier studies carotid stenosis was found to be associated with higher Neopterin concentrations. In that study as in ours, the great majority of Neopterin concentrations found were well within the normal range of healthy controls. Our data point to a role of H. pylori to induce a long-lasting albeit moderate deterioration of the cellular immune system, which may contribute to increase the risk of atherosclerosis.
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Neopterin: A Prognostic Variable in Operations for Lung Cancer
The Annals of thoracic surgery, 2000Co-Authors: Rupert Prommegger, Dietmar Fuchs, Bernhard Widner, Christian Murr, Andreas Unger, G. M. SalzerAbstract:Abstract Background . We studied the prognostic value of preoperatively measured Neopterin to predict survival of lung cancer patients. Neopterin is produced and secreted by interferon-γ-stimulated monocytic cells. High urinary Neopterin concentrations are found in patients with viral infections, allograft rejection episodes, and some malignant diseases. In various tumor types high urinary Neopterin concentrations are associated with a worse prognosis. Methods . Preoperative Neopterin levels of 110 patients (29 women, 81 men) with lung cancer including 7 patients with small cell lung cancer were measured and related to the time of survival after operation. Patients with clinically suspected stage IIIB lung cancer were not operated and therefore not enrolled in this study. Infectious diseases were not apparent at the time of preoperative urine sampling. Median postoperative follow-up period was 17.4 months. Results . In a univariate analysis, patients with a preoperative Neopterin concentration of more than 212 μmol/mol creatinine (4th quartile) were determined to have a significantly lower survival probability. In a multivariate analysis, a Neopterin concentration of more than 212 μmol/mol creatinine ( p p Conclusions . Preoperative Neopterin proved to be a reliable prognostic factor for survival. Immunology may provide an accurate assessment of tumor aggression and its clinical behavior. In this sense, Neopterin can serve as an immunologically based estimation of malignant outgrowth. In patients who are operable by clinical tumor stage but have a high risk for operation, elevated preoperative Neopterin may help in the decision for a nonoperative treatment.
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Neopterin is an independent prognostic variable in females with breast cancer
Clinical Chemistry, 1999Co-Authors: Christian Murr, Anton Bergant, Martin Widschwendter, K Heim, H Schrocksnadel, Dietmar FuchsAbstract:Background: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-γ, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in Neopterin in the serum and urine of patients depends on tumor stage and type. Methods: In a retrospective study comprising 129 females with breast cancer, urinary Neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. Results: Urinary Neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases ( P <0.05) and by tumor differentiation ( P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases ( P <0.001), Neopterin ( P <0.001), tumor size ( P = 0.001), and lymph node status ( P <0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases ( P <0.001), Neopterin ( P <0.01), and lymph node status ( P <0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased Neopterin concentrations was 2.5 compared with patients with Neopterin concentrations within the reference interval. Conclusion: Urinary Neopterin provides additional prognostic information in patients with breast cancer.
Helmut Wachter - One of the best experts on this subject based on the ideXlab platform.
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Factors influencing serum Neopterin and β2-microglobulin levels in a healthy diverse population
Journal of Clinical Immunology, 1994Co-Authors: Laura S. Diamondstone, Helmut Wachter, Dietmar Fuchs, David J. Tollerud, Linda Morris Brown, Elizabeth Maloney, Carole C. Kurman, David L. Nelson, William A. BlattnerAbstract:Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing Neopterin and β2-microglobulin (β2m) values. Both Neopterin and β2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: Neopterin, 5.06 vs 4.49 nmol/L; β2m, 1.36 vs 1.28 mg/L). Gender differences were noted for β2m but not Neopterin values (β2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and β2m were correlated in this healthy adult population (adjusted r =0.53, P =0.001), yet no other interrelationships with numerous biologic markers except between β2m and serum-soluble interleukin-2 receptor levels (adjusted r =.41, P =0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing Neopterin or β2m levels.
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the role of Neopterin as a monitor of cellular immune activation in transplantation inflammatory infectious and malignant diseases
Critical Reviews in Clinical Laboratory Sciences, 1992Co-Authors: Dietmar Fuchs, Gilbert Reibnegger, Gunter Weiss, Helmut WachterAbstract:The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of Neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of Neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased Neopterin levels indicate endogenous formation of gamma interferon, and monitoring of Neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection Neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, Neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases Neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of Neopterin measurements agree with the important role that the cellular immune system plays in these disorders.
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Predictive Value of Interleukin-6 and Neopterin in Patients with Multiple Myeloma
Cancer Research, 1991Co-Authors: Gilbert Reibnegger, Michael Krainer, Helmut Wachter, Heinz Ludwig, Manfred Herold, Heinz HuberAbstract:Abstract Concentrations of interleukin-6 and Neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both Neopterin ( P = 0.0008) and interleukin-6 ( P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and Neopterin was weak but significant (Spearman9s rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both Neopterin ( P = 0.0001) and interleukin-6 ( P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and Neopterin or Neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, Neopterin remained significant in all multivariate models.
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Postmortem evaluation of serum and urine Neopterin concentrations.
Journal of forensic sciences, 1991Co-Authors: E. Ambach, Gilbert Reibnegger, Dietmar Fuchs, W. Tributsch, R. Henn, Helmut WachterAbstract:REFERENCE: Ambach, E., Tributsch, W., Fuchs, D., Reibnegger, G., Henn, R., and Wachter, H., "Postmortem Evaluation of Serum and Urine Neopterin Concentrations," Jour- nal of Forensic Sciences, JFSCA, Vol. 36, No. 4, July 1991, pp. 1089-1093. ABSTRACT: Cellular immune response is accompanied by the release of Neopterin. Increased Neopterin levels in urine and serum are observed in patients during viral infections, autoim- mune diseases, and allograft rejections and certain malignant diseases. We investigated post- mortem Neopterin concentrations in urine and serum samples taken from 32 corpses 3 to 69 h (mean 19.3 h) after death. Urine Neopterin concentrations in corpses are similar to those of healthy live controls and are independent of the time after death. In contrast, serum Neopterin concentrations are frequently greatly increased in corpses, and the levels are higher in sera collected more than 10 h after death in comparison with samples obtained earlier. Neopterin measurement in urine and serum samples of corpses is feasible. It appears likely that urine Neopterin concentrations could aid the diagnosis of inflammatory diseases in corpses.
C.a. Holden - One of the best experts on this subject based on the ideXlab platform.
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Increased urine Neopterin levels in psoriasis.
The British journal of dermatology, 1992Co-Authors: C.c. Harland, R.p. Whitaker, J.l. Barron, C.a. HoldenAbstract:Summary The production of Neopterin closely reflects activation of T-lymphocyte-mediated immunity. Oxidized and reduced forms of urine Neopterin were measured by reversed-phase ion-pair high-performance liquid chromatography in patients with moderate to severe chronic plaque psoriasis (n= 14), and in a heterogeneous group of patients (n= 14) with cutaneous T-cell malignancies (CTCM). Results were compared with healthy non-psoriatic control subjects (n= 30). Neopterin levels were repeated after a course of ultraviolet B therapy (UVB) plus topical tar or dithranol, or photochemotherapy (PUVA), in 12 psoriatic patients. Fully oxidized urine Neopterin levels and Neopterin/creatinine ratios were significantly elevated in the psoriatic group compared with controls (P < 0·002, P < 0·05) but not in the CTCM group. Both Neopterin and its creatinine ratio were significantly reduced by treatment (P < 0·05, P < 0·01). Psoriasis area and severity index scores (PASI) correlated strongly with urine Neopterin levels (P < 0·001). These findings indicate that urine Neopterin concentrations may be a marker of psoriatic disease activity, and further support the importance of activated T lymphocytes in the pathogenesis of psoriasis.