Is there any relationship between serum and urine neopterin and serum interferon-�� levels in the activity of Behcet's disease? (original) (raw)
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Journal of Translational Medicine, 2011
Background Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months. Methods RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests. Results Neopterin (p < 0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p < 0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p < 0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation. Conclusions Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.
BioTechnologia, 2012
Neopterin, a marker of stimulated cellular immune response, levels increase during many disorders. A number of different features of neopterin prompted us to study its serum concentration in patients with all stages of chronic kidney disease (CKD) and patients with coronary artery disease (CARD). To the best of our knowledge this is the first study that evaluates and compares the serum neopterin concentration in those diseases taken together as one study. One hundred and twenty five subjects, divided into five groups, were included in the study. The first three groups consisted of patients with different stages of CKD. CARD patients without CKD and healthy volunteers as controls were also studied. Serum neopterin concentration was measured by an enzyme-linked immunosorbent assay (ELISA, BRAHMS, Hennigsdorf/Berlin, Germany) according to the manufacturers' instructions. We have found that patients with the most advanced stage of CKD had fifteen times higher serum neopterin than patients from other studied groups. Interestingly, in the CKD1-2, CKD3-4 and CARD patients without CKD, serum neopterin concentrations were similar to those obtained from healthy volunteers. Serum urea and serum ferritin appeared to be significant independent predictors of serum neopterin concentration after adjustment for urea, CA-IMT, peripheral systolic blood pressure, ferritin, hsCRP, HD vintage, BMI and eGFR, explaining 95.89% of serum neopterin variations. In conclusion, it seems that despite the existence of many factors that may influence serum neopterin, those derived from impaired renal function and immunological disturbances coming from hemodialysis treatment are crucial. In this study, we observed that the more impaired the renal function, higher is the increase in serum neopterin concentration.
Talanta, 2003
Twelve self-sustaining nonagenarians, 10 women and two men, aged 949/3 years, and eight institutionalised nonagenarians, eight women, aged 919/1 year as well as 11 control subjects, seven women and four men, aged 849/5 years entered the study. Urinary neopterin, an indicator of systemic immune activation, and serum thiobarbituric acid reactive substances (TBARS), a marker of lipoperoxidation, were determined initially, and collection of the blood and urine samples was repeated at 3-month interval. Neopterin was measured in the urine specimens by reversed-phase high performance liquid chromatography. A C 18 reversed-phase column 3.3)/150 mm, 5 mm-diameter packing Separon SGX was used. Potassium phosphate buffer (15 mmol l (1 , pH 6.4) at flow rate of 0.8 ml min (1 was used as mobile phase. After centrifugation (5 min, 1300)/g) and diluting 100 ml of urine specimens with 1.0 ml of mobile phase containing 2 g of disodium Á/EDTA per litre, a 20 ml sample was injected on a column. Neopterin was identified by its native fluorescence (353 nm excitation, 438 nm emission). Creatinine was determined by Jaffé kinetic reaction after dilution of sample 1:50 (v/v). The concentration of neopterin in urine was expressed as neopterin/creatinine ratio (mmol mol (1 creatinine). TBARS were determined spectrofluorometrically using LS-5 spectrofluorimeter (excitation wavelength 528 nm, emission wavelength 558 nm) after extraction with n-butanol treatment with thiobarbituric acid. The significance of differences between nonagenarians and control group was examined by ANOVA Á/Kruskal Á/ Wallis tests, using statistical software NCSS 6.0.21 (Kaysville, UT, 1996). The decision on significance was based on P0/0.05. Urinary neopterin was significantly higher in institutionalised compared to self-sustaining subjects and controls (6259/565 vs. 2039/63 mmol mol (1 creatinine, and 1989/128 mmol mol (1 creatinine, respectively, P0/0.006). The serum TBARS were higher in both groups of nonagenarians (3.239/1.16 mmol l (1 and 2.699/0.39 vs. 2.129/0.83 mmol l (1 for the self-sustaining, institutionalised and controls, respectively, P0/0.023). We conclude that the
Neopterin in patients with chronic kidney disease and patients with coronary artery disease
Biotechnologia. Journal of Biotechnology, Computational Biology and Bionanotechnology, 2012
Neopterin, a marker of stimulated cellular immune response, levels increase during many disorders. A number of different features of neopterin prompted us to study its serum concentration in patients with all stages of chronic kidney disease (CKD) and patients with coronary artery disease (CARD). To the best of our knowledge this is the first study that evaluates and compares the serum neopterin concentration in those diseases taken together as one study. One hundred and twenty five subjects, divided into five groups, were included in the study. The first three groups consisted of patients with different stages of CKD. CARD patients without CKD and healthy volunteers as controls were also studied. Serum neopterin concentration was measured by an enzyme-linked immunosorbent assay (ELISA, BRAHMS, Hennigsdorf/Berlin, Germany) according to the manufacturers’ instructions. We have found that patients with the most advanced stage of CKD had fifteen times higher serum neopterin than patien...
Association between Serum Neopterin and Inflammatory Activation in Chronic Kidney Disease
Background. The serum levels of neopterin, amarker associated with cell-mediated immunity are elevated in chronic kidney disease (CKD). We evaluated serum neopterin levels and investigated its association with markers of inflammation in a cross-section of CKD subjects without known cardiovascular disease. Methods. Serum neopterin levels were measured in 118 patients with stage 3–5 CKD and 41 healthy subjects with normal kidney function (HC). Patients with known cardiovascular disease were excluded. We also estimated highly sensitive CRP (hsCRP) and interluekin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the CKD subjects. All assays were done using commercially available ELISA kits. The correlation between neopterin and markers of inflammation were investigated. Results. Of the CKD population, 82 were in stage 5 (60 stage 5 D), 24 in stage 4, and 12 in stage 3. The mean age was 51.04 ± 1.3 years and 66% were males. The commonest cause of CKD was diabetes (36%). Serum neopterin levels were 5-fold higher in CKD patients as compared to HC (74.8 ± 3.6 versus 15.0 ± 2.8 nmol/L, P < 0.0001). There was a graded increase of serum neopterin from stages 3 to 4 and 5. CKD 5 D patients exhibited significantly higher levels compared to nondialysis stage 5 patients (P < 0.0001). An inverse correlation was noted between serum neopterin and eGFR (r = −0.359, P < 0.0001). Serum neopterin correlated with hsCRP (r = 0.285, P = 0.002), IL-6 (r = 0.212, P = 0.034), and IFN-γ (r = 0.32, P = 0.001) but not with TNF-α. Conclusion. Serum neopterin level is elevated and correlates with the severity of CKD. The elevation correlates with elevation ofmost, but not all, inflammatory markers. Its role in future development of cardiovascular disease and modulation with anti-inflammatory therapies needs further studies.
Urinary neopterin concentrations vs total neopterins for clinical utility
Clinical chemistry, 1989
Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for cli...
Brain, 1997
The aim of this study was to assess neopterin, a marker of and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls interferon gamma (IFN-γ) induced macrophage activity, as (P Ͻ 0.001 for all patients and P Ͻ 0.01 for each group); a possible surrogate marker of inflammation in patients with the meansϮSD peaks/subject/month were: 2.1Ϯ1.8; 3.0Ϯ1.7; multiple sclerosis. Urinary neopterin to creatinine ratios 3.3Ϯ 2.3 and 0.2Ϯ 0.6 for PP, RR, SP patients and controls, (UNCRs) were measured daily in 10 primary progressive respectively. Nine relapses occurred in nine patients during (PP), 10 relapsing remitting (RR) and 11 secondary the study, and all were associated with increased neopterin progressive (SP) patients with multiple sclerosis, and 14 excretion, which tended to be greater than that on days not normal control (NC) subjects, for periods of up to 12 associated with a relapse. Three of the nine relapses were weeks. After excluding measurements related to infection, preceded by an upper respiratory tract infection. In eight out the median of the individuals' average UNCRs was of 13 patients who had infections during the study, increased significantly higher in patients than in controls (P Ͻ 0.001 neopterin excretion was noted for periods of up to 6 weeks for all patients and P Ͻ 0.01 for each of the three groups post-infection, significantly longer than that which occurred of patients); the median UNCRs (and interquartile ranges) after infections in controls. This confirms infection as a were 187 (135-231), 187 (165-277), 218 (164-517) and 134 potent inducer of symptomatic and asymptomatic disease (97-152) µmol/mol for PP, RR, SP patients and controls, activity in mutiple sclerosis, and provides further support of respectively. Similarly, patients had a greater median a pivotal role for IFN-γ in the pathogenesis of mutiple proportion of days with a UNCR above normal (P Ͻ 0.001 sclerosis. Urinary neopterin excretion is increased in patients for all patients and P Ͻ 0.01 for each group); the median with both progressive and relapsing mutiple sclerosis, and percentages (and interquartile ranges) were 16 (6-62), 28 therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis disease activity. (21-36), 49 (14-86) and 0 (0-6)% for PP, RR, SP patients Abbreviations: EDSS ϭ expanded disability status scale; IFN-γ ϭ interferon gamma; PP ϭ primary progressive; RR ϭ relapsing remitting; SP ϭ secondary progressive; TNF-α ϭ tumour necrosis factor alpha; UNCR ϭ urinary neopterin to creatinine ratio
The Egyptian Journal of Hospital Medicine
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 that the 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 parameters then estimation of serum neopterin levels seems beneficial in the assessment of disease activity and evaluation of the efficacy of various treatment regimens used.
Neopterin and Interferon-Gamma as Immune Response Markers in Betathalassemia Major Patients
Asian Journal of Pharmaceutical and Clinical Research, 2018
Objective: The assessment of neopterin and interferon-gamma (IFN-γ) levels as a part of immune system response about serum iron status in β-thalassemia (TM) major patients.Methods: Spectrophotometry applied for the estimation of iron status including serum iron level, total iron-binding capacity, and unsaturated iron-binding capacity. Enzyme-linked immunosorbent assay (ELISA) applied for the estimation of the serum cytokines included neopterin and IFN-γ also serum ferritin estimation by ELISA from 130 β-TM major patients where they divided according to serum ferritin level (< and ≥2500 ng/mL).Results: The neopterin and IFN-γ concentration showed significantly increased with direct correlation among TM patient group when compared to the normal healthy control group. However, there was no significant difference between different levels of serum ferritin.Conclusion: The increased serum level of neopterin and IFN-γ found in patients with β-TM may be due to the direct effect of iron o...