Clinical and laboratory features of HTLV-I asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis from the Brazilian Amazon

ABSTRACT Clinical and laboratory parameters including blood and cerebrospinal fluid (CSF) neopterin were investigated in human-T-lymphotropic-virus-type-I associated-myelopathy/tropical-spastic-paraparesis-HAM/TSP and in HTLV-I carriers. HAM/TSP (n = 11, 2 males/9 females, median age = 48 years), recently diagnosed HTLV-I carriers (n = 21, 15 females/6 males, median age = 44 years), healthy individuals (n = 20, 10 males/10 females, median age = 34.6 years) from the Brazilian Amazon (Manaus, Amazonas State) were investigated. Neopterin was measured (IBL ELISA Neopterin, Germany) in serum samples of all the participants, in CSF of 9 HAM/TSP patients as well as in 6 carriers. In HAM/TSP patients, CSF cell counts, protein and glucose were measured, the Osame’s motor-disability-score/OMDS was determined, and brain/spinal cord magnetic-resonance-imaging (MRI) was performed. HAM/TSP patients had normal CSF glucose, leukocyte counts; and normal protein levels predominated. Brain-MRI showed white-matter lesions in 7 out of 11 HAM/TSP patients. OMDS varied from 2-8: 9 were able to walk, 2 were wheel-chair-users. The median serum neopterin concentration in HAM/TSP patients was 6.6 nmol/ L; min. 2.8- max. 12.5 nmol/ L); was lower in carriers (4.3 nmol/L; min. 2.7- max. 7.2 nmol/ L) as well as in healthy participants (4.7 nmol/ L; min. 2.7- max. 8.0 nmol/ L) (p < 0.05). CSF neopterin concentrations in HAM/TSP patients were higher than in serum samples, and higher compared to carriers (p < 0.05). Carriers had similar serum-CSF neopterin concentrations compared to healthy participants. Variable clinical and laboratory profiles were seen in HAM/TSP patients, however our results support the neopterin measurement as a potential biomarker of disease activity.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity / Associação de neopterina como marcador de ativação do sistema imunológico e atividade da artrite reumatoide juvenil

OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p < 0.05). A statistically significant higher mean level serum neopterin concentration (p < 0.05) was found in JIA patients (20.43 ± 8.73 nmol/L) than in controls (6.88 ± 2.87 nmol/L) (p < 0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-a, IL-6, MCP-1, and JADAS-27 (p < 0.05). No correlation was found between serum neopterin and CRP (p > 0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05).CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

OBJETIVO: Avaliar as concentrações plasmáticas de neopterina em pacientes com artrite idiopática juvenil (AIJ) ativa e correlacioná-las com a atividade da doença.MÉTODOS: Foram recrutados da clínica de Alergia e Imunologia Infantil da Universidade Ain Shams 60 pacientes diagnosticados com AIJ ativa, bem como 60 crianças aparentemente saudáveis com a mesma idade e o mesmo sexo no grupo de controle. A atividade da doença foi avaliada pelo Escore de Atividade da Doença da Artrite Juvenil em 27 Articulações (JADAS-27). Foram feitas investigações laboratoriais em todos os pacientes, incluindo a determinação da concentração de hemoglobinas, a taxa de sedimentação de eritrócitos e a proteína C-reativa. Foram mensuradas as concentrações séricas do fator de necrose tumoral alfa, interleucina-6 e proteína quimiotática de monócitos-1 e neopterina.RESULTADOS: Foi encontrada uma diferença significativa entre os pacientes com AIJ e os controles quanto às médias de Hb, TSE, FNT-a, IL-6 e MCP-1 (p < 0,05). Foi encontrado um nível estatística e significativamente maior de concentração média de neopterina sérica (p < 0,05) em pacientes com AIJ (valor médio de 20,43 ± 8,73 nmol/L) do que em controles (valor médio de 6,88 ± 2,87 nmol/L) (p < 0,05). Foram detectadas correlações positivas significativas entre a neopterina sérica e TSE, FNT-a, IL-6, MCP-1 e JADAS-27 (p < 0,05). Não foi encontrada correlação entre a neopterina sérica e a PCR (p > 0,05). A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05).CONCLUSÃO: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ.

Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease

PURPOSE: We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core. CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.

Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection

BACKGROUND: Fever as a common presenting complaint in pediatric patients can be due to various causes. Differentiating bacterial infection from other causes is important because the prompt use of antibiotics is critical in bacterial infection. Traditional markers of infection such as BT and WBC count may be unspecific and culture may be late or absent. CRP and Procalcitonin (PCT) have been considered to evaluate the evolution of infections and sepsis in patients presenting with SIRS. Neopterin has also been proposed to aid in the diagnosis of bacterial infection. In this study, we compared the value of the serum PCT, neopterin level, and WBC count for predicting bacterial infection and outcome in children with fever. METHODS: 158 pediatric (2-120-month-old) patients suspected to have acute bacterial infection, based on clinical judgment in which other causes of SIRS were ruled out were included in the study. WBC count with differential was determined and PCT and neopterin levels were measured. RESULTS: PCT level was higher in bacterial infection and patients who were complicated or expired. CONCLUSION: Rapid PCT test is superior to neopterin and WBC count for anticipating bacterial infection, especially in ED where prompt decision making is critical. ABBREVIATIONS: BT, body temperature; WBC, white blood cell; PCT, procalcitonin; CRP, C-reactive protein; SIRS, systemic inflammatory response syndrome; ED, emergency department.

Incomplete immunological recovery following anti-tuberculosis.

Background & objectives: Mycobacterium tuberculosis infection has been shown to result in increased HIV replication and disease progression in HIV-infected individuals through increased immune activation. The objective of this study was to correlate plasma levels of immune activation markers with the presence of tuberculosis (TB) in HIV-infected and uninfected individuals, and to study the changes following anti-tuberculosis treatment. Methods: Plasma markers of immune activation - neopterin, beta-2-microglobulin (β2M) and soluble tumour necrosis factor alpha receptor type I (sTNFα-RI) were measured by ELISA in 42 HIV positive TB patients (HIV+TB+) undergoing a six-month course of TB chemotherapy. Thirty seven HIV+ persons without active TB, 38 TB patients without HIV infection, and 62 healthy volunteers served as controls. Results: Plasma levels of all three markers were elevated in HIV+ individuals, more so in those with active TB. When HIV+ individuals were further categorized based on CD4+ T cell counts, HIV+TB+ patients with CD4+ T cells counts < 200 cells/μl were found to have the highest levels at baseline with a steep fall in neopterin and sTNFα-RI during treatment, but in most instances the levels did not drop to normal. β2M levels remained persistently high despite completing TB treatment. Interpretation & conclusions: The fi ndings of the study suggest that both HIV and TB act synergistically to activate the host immune system. Although ATT was effective in clearing M. tuberculosis infection, a high proportion of HIV+ TB patients continued to have levels well above the normal range, indicating that underlying immune activation persists despite TB treatment. None of the markers were specific enough to be used to assess cure of TB.

Plasma neopterin and peroxide levels in pulmonary tuberculosis patients on chemotherapy with or without micronutrient supplementation

Neopterin and H2O2 are products of cellular [macrophage] activation. The exact roles of these secretions by activated macrophages in protection against tuberculosis remain unclear. In the present study, the changes in the levels of neopterin and total plasma peroxides [TPP] were assessed in pulmonary tuberculosis [PTB] patients on chemotherapy with [C+M] or without [C- M] micronutrient supplementation. Thirty-eight newly diagnosed PTB patients were selected for this study. Twenty patients were treated with anti-tuberculosis drugs and micronutrient [C+M] while 18 PTB-patients were treated with only anti-tuberculosis chemotherapy [C-M]. Plasma neopterin and TPP concentrations were measured by enzymes linked immunosorbent assay [ELISA] and colorimetric method respectively. All PTB patients had elevated neopterin [p=0.02] and TPP [p=0.00] levels when compared with the non-PTB controls. Plasma level of neopterin and TPP declined significantly in C+M after 2 weeks of treatment [p= 0.00, p=0.01 respectively] and also after 4 weeks of treatment [p = 0.01 and p=0.00 respectively] when compared with baseline levels before treatment. No significant change was observed in the levels of neopterin and TPP in C-M after 4 weeks of treatment when compared with baseline value before treatment. Micronutrient supplementation enhanced the decline in the levels of neopterin and TPP after two weeks of treatment. Chemotherapy alone did not produce significant reduction. Therefore, micronutrient supplementation of PTB drugs with synthetic antioxidants or naturally occurring ones [fruits and vegetables] should be attempted

Serum neopterin and zinc levels as biological markers of the HCV disease progression

In chronic hepatitis C virus [HCV] infection, both oxidative stress and the effectiveness of the host immune response contribute to its progression to cirrhosis and the development of hepatocellular carcinoma [HCC]. Neopterin is produced by monocyte-derived macrophages after stimulation with interferon-gamma [IFN- gamma] released from activated T- lymphcytes or other immune activators. High neopterin production is associated with increased production of reactive oxygen species [ROS]. Zinc plays an important role in cell-mediated immune function and it has also anti inflammatory and antioxidant properties which can neutralize free radicals and may protect liver cells from the potential damage they cause. To investigate the relationship between serum levels of neopterin and immune-regulated micronutrients [Zn] with chronic HCV infection progression mediated by increased cellular oxidative stress [malondialdehyde, MDA]. The study included 60 subjects that were divided into two groups: Group I comprised 40 chronic HCV patients further subdivided according to liver biopsy inflammatory grading into: 18 patients with mild active hepatitis [Ia], 16 patients with moderate active hepatitis [Ib] and 6 patients with liver cirrhosis [Ic]. Group II comprised 20 healthy volunteers as control. Serum Zinc was measured by atomic absorption spectrophotometer [AAS], neopterin by ELISA and MDA by colorimetric method. Serum levels of neopterin and MDA were detected significantly higher in HCV patients than controls. A significant positive correlation was detected between the levels of both markers with the levels of total bilirubin, AST, ALT in HCV patients. Serum levels of neopterin and MDA were significantly elevated in group Ib and Ic HCV patients compared with group la patients, significant low serum level of zinc were detected in HCV patients than controls and were significantly lower in group Ib and Ic HCV patients than group Ia patients. Serum zinc, neopterin and MDA levels may be valuable biomarkers for the assessment of severity of viral hepatic damage in HCV infection

Correlation between old and new immuno-inflammatory markers and disease activity in systemic lupus erythematosus

To compare new SLE activity inflammatory markers with traditional ones. In addition, to correlate those with disease activity index of SLE. Forty-three patients fulfilling the American College of Rheumatology criteria for diagnosis of SLE and 20 apparently healthy controls were subjects for study. Neopterin, soluble intercellular adhesion molecule [sICAM-1] and soluble vascular cell adhesion molecule [sVCAM-1] were measured as well as anti-dsDNA antibodies, C3, C4 and CRP. The British Isles Lupus Assessment Group [BILAG] disease activity index was used to measure disease activity. Twenty-four [55.8%] patients had active SLE [total BILAG score > 5], involving more than one system in nine [37.5%]. Activity was more in musculoskeletal, mucocutaneous, and hematological systems. All markers showed significant differences between SLE patients and controls. Neopterin, sVCAM and CRP were highest when compared to controls [p>0.001] as well as to inactive subgroup. The level of sICAM-1 in active was insignificantly higher than inactive group. Significant correlations were found between total BILAG score and CRP, neopterin, sVCAM. No positive correlation was found between any marker and disease activity of different BILAG organ systems. All tests were done for 22 patients on 3 occasions over 6 months. Highest levels of sVCAM-1 were in active subgroup with flares during the first measurement. Significant decrease between first and third measurement was observed within all subgroups. Neopterin and sVCAM-1 appear to be clinically useful for isolated and serial concentrations assessments of SLE disease activity scored using the BIIAG index. Anti-dsDNA and sVCAM-1 are good markers to predict remission

Serum neopterin as a marker of severity of unstable angina

The current study aimed to assess serum neopterin level in patients with chronic stable angina and unstable angina and to assess the relation between neopterin concentration and complex coronary artery stenosis in patients with unstable angina. There is increasing evidence that inflammation plays an important role in atherogenesis and may determine plaque vulnerability. At angiography, disrupted or ulcerated plaques appear as complex stenosis. Plaque vulnerability has been shown to be a function of the increased local number of inflammatory cells within plaques, particularly activated macrophages and lymphocytes. Neopterin is a pterydine derivative produced by activated macrophages, so it can be used as a marker for severity in patients with unstable angina. Fourty patients were involved in this study [30 patients with the diagnosis of unstable angina and 10 patients with the diagnosis of chronic stable angina], ten healthy subjects of matched age and sex were involved as control group. All members of the study were subjected to complete medical history, general and local cardiac examination, 12 lead ECG, echocardiography, and the following laboratory investigations: CK and CKMB, C-reactive protien, Neopterin level, serum cholesterol, LDL, HDL, triglycerides, creatinine, urea and blood glucose. Coronary angiography was done to all members of group 1 [patients with the diagnosis of unstable angina]. Our study revealed that: Neopterin level was significantly higher in patients with ischaemic heart disease than in healthy controls. It was also significantly higher in patients with unstable angina than in patients with chronic stable angina. Neopterin and CRP levels were significantly correlated with the presence of multiple complex lesions in angiography. There is a strong association between neopterin level and the number of complex lesions in angiography in patients with unstable angina, so, it can be used in risk stratification in these patients

Neopterin levels in patients with post hepatitis C chronic liver disease

Hepatitis C virus causes biochemical, immunological and histological changes in host immuno response against the virus. Neopterin [NPT] is a valuable marker of cell-mediated immunity that reflects the degree of T helper-1 [Th-I] immune activation. Evaluation of the significance of serum neopterin as a marker of cellular immune response in patients with different states of post hepatitis C chronic liver disease. Seventy patients with post hepatitis C chronic liver disease were included in the current study: 40 patients with chronic hepatitis C and 30 patients with liver cirrhosis in addition to 15 healthy individuals as a control group. Patients were assessed and evaluated by laboratory instigations and liver biopsy to determine the severity of the disease. Serum neoterin level was significantly elevated in patients with chronic hepatitis C virus infection and cirrhosis compared to the control group with distinctly higher concentrations in the cirrhotic stage than those in he non-cirrhotic stage of disease. Neopterin may be an early and valuable biochemical marker of cellular immunity which is activated upon simulation of cells by interferon. Measurements of immune activation by NPT could potentially be helpful surrogate markers in progression of liver disease

Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment.

Most patients with liver cancer are diagnosed when they are not suitable for resection. Although some palliative approaches can be applied to these patients, the overall survival rate remains unsatisfactory. Active hexose correlated compound (AHCC), a newly developed functional food, has been shown to act as a potent biological response modifier in in vitro experiments. Recently, AHCC was found to improve the prognosis of hepatocellular carcinoma patients following surgical treatment. We investigated whether AHCC could prolong survival and improve the prognosis of patients with advanced liver cancer. A prospective cohort study was performed with 44 patients with histologically confirmed liver cancer. All of the patients underwent supportive care. Survival time, quality of life, clinical and immunological parameters related to liver function, cellular immunity, and patient status were determined. Of the 44 patients, 34 and 10 received AHCC and placebo (control) orally, respectively. Patients in the AHCC treated-group had a significantly prolonged survival when compared to the control group by Mann-Whitney test (95% CI, p = 0.000). Quality of life in terms of mental stability, general physical health status, and ability to have normal activities were significantly improved after 3 months of AHCC treatment when tested using the Wilcoxon signed-rank test (on one-sided test, p = 0.028, 0.037, and 0.040, respectively). The apparent different clinical parameters between the two groups were the levels of albumin and percentage of lymphocytes with p-values of 0.000 and 0.026 at 1 and 2 months after treatment, respectively. Unlike the control patients, AHCC treated-patients with longer survival time had the tendency of better outcomes since the levels of AST and ALT had not increased rapidly from their baselines at follow-up. In addition, the levels of total IL-12 and neopterin were slightly increased in AHCC treated-patients. This study suggests that AHCC intake could prolong the survival and improve the prognosis of patients with advanced liver cancer and delay the gradual decline of their physiological status.

The Clinical Significance of Serum and Urinary Neopterin Levels in Several Renal Diseases

Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker associated with cell-mediated immunity in various diseases. We hypothesized that the levels of serum and urine neopterin would be elevated in renal disease, and would correlate with certain clinical parameters. We evaluated serum and urinary neopterin levels in patients with several renal diseases, including nephrotic syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with CRF and ESRD, as compared to controls. Urinary neopterin levels were also found to be elevated in patients with CRF and ESRD, as compared to controls. Serum neopterin levels showed significant positive correlation with age, serum BUN and creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, serum albumin and total iron binding capacity. Urine neopterin levels exhibited positive correlation with age and serum creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In conclusion, increased serum and urinary neopterin levels were found in some patients with renal disease and were correlated with certain clinical parameters.

Serum neopterin levels in HIV infected patients with & without tuberculosis.

BACKGROUND & OBJECTIVE: Three categories of prognostic markers are best documented as having significance in relation to prognosis of HIV infection. These include HIV viral load, CD4 T-cell levels and plasma levels of soluble markers of immune activation. The plasma activation markers, like neopterin, tumor necrosis factor alpha (TNF-alpha), interleukins etc., are products of cytokine activity and represent immunologic changes throughout the body. There is not much information available on serum neopterin estimation in patients infected with both HIV and tuberculosis (TB), though neopterin levels are known to be elevated in pulmonary TB patients. In this study we attempted to correlate neopterin levels with the presence of tuberculosis in HIV infected and uninfected individuals and studied the changes after antituberculosis treatment. METHODS: Serum neopterin concentrations were measured by high performance liquid chromatography (HPLC) in 25 HIV-seropositive (HIV-TB) and 10-seronegative (TB) patients with tuberculosis before, during and at the end of antituberculosis therapy (ATT). S-neo was also measured in 10 HIV-seropositive asymptomatic individuals and 10 healthy controls. The results were correlated with clinical, bacteriological and immunological status. RESULTS: All TB patients regardless of HIV status had elevated s-neo concentrations at diagnosis, which declined gradually during treatment. Patients with HIV/TB with CD4 counts < 200/mm(3) had the highest levels at baseline with a steep fall during treatment. The median level at the end of treatment was significantly higher in HIV/TB than in TB patients, despite clinical improvement and bacteriological clearance of Mycobacterium tuberculosis. HIV infected asymptomatic individuals had neopterin levels that were higher than healthy controls but lower than HIV-TB patients. INTERPRETATION & CONCLUSION: Serum neopterin levels are elevated in HIV-positive patients, with the highest levels in those with tuberculosis and CD4 counts < 200/mm(3). Though the levels decrease with anti tuberculosis therapy, persistently elevated levels indicate progressive HIV disease and a poor prognosis.

Role of serum neopterin level in unstable angina

Coronary artery disease is the most common form of heart disease and the important single cause of death. Unstable angina is a life threatening disorder and a major cause of emergency medical care. Disruption of vulnerable atheromatous plaque is the most common pathogenic mechanism in unstable angina. Macrophage and T cell lymphocytes are critical in the growth and changes of plaques through the secretion of growth factors, cytokines and extracellular matrix digesting enzymes, which weaken fibrous cap. Neopterin, which is a byproduct of guanosine triphosphate degradation in macrophages activated by interferon gamma being a marker of macrophage activation, is a more direct measurement of immune system activation. Immune system activation may play a pathogenic role in acute coronary syndrome. Neopterin can be used as a marker for activity of coronary disease. The purpose of this study to evaluate the neopterin level in patients had unstable angina and complex coronary artery disease lesions vs. patient with chronic stable angina. Prospective study was performed in 50 patients divided in three groups. Group1: [30 patients with unstable angina class IIIb according to Braunwald classification. Group2: 10 patients with chronic stable angina. Group3: 10 patients with normal coronary angiography. The neopterin level was high significantly in group 1 in compare to both other two groups. There was correlation between the neoperin level and the number of angiographically complex lesion. Neopterin level was not correlated vessel score or stenosis score

Serum neopterin level in patients with coronary artery ectasia with or without stenosis

Coronary artery ectasia [CAE] is an uncommon angiographic finding, the prevalence in most series ranges from 1.2% to 5.3%. CAE was defined as arterial segment with a diameter of at least 1.5 times the diameter of adjacent normal coronary artery segment. Atherosclerosis is the most common cause of CAE and there is a high association of CAE with stenotic coronary artery disease. CAE is not an innocent condition even in the patients with pure ectasia without stenosis. It may present by chronic stable angina pectoris, unstable angina, myocardial infarction and heart failure. Immune cells appear to be critical in development of atherosclerosis. High levels of neopterin were found in patients with chronic stable angina pectoris and acute coronary syndromes. Correlation of serum neopterin levels to the presence of CAE in patients with stable coronary artery disease. Forty patients referred to cardiac catheterization unit for evaluation of typical stable angina pectoris, were divided into three groups: Group A [15 patients] of pure ectasia, Group B [15 patients] of CAE associated with stenosis and Group C [10 patients] of stenotic lesions only. Each patient in the three groups was subjected to coronary angiography, and measurement of serum neopterin level by ELISA technique. Neopterin levels were elevated in the three studied groups but were significantly higher in patients with two and three vessels lesions than in patients with one vessel lesion. Also neopterin levels were significantly higher in ectasia with slow flow than in ectasia without slow flow. Inflammation seems to play a major role in the etiology of CAE as well as coronary artery stenosis. Neopterin level is related to the severity of the disease. Also it seems that there is more activation of the immune system in ectasia with slow flow than in ectasia without slow flow as neopterin level was higher in ectasia with slow flow than ectasia without slow flow

Serum neopterin, tumor necrosis factor-alpha and soluble tumor necrosis factor receptor II [p75] levels and disease activity in patients with systemic lupus erythematosus

This study was undertaken to determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-alpha [TNF-alpha] and soluble tumor necrosis factor receptor II [p75] [sTNFRII] and the development of major flares [active disease] in patients with systemic lupus erythematosus [SLE] manifested clinically with lupus nephritis [LN], neuropsychiatric lupus erythematosus [NPLE] or vasculitis. Patients and Serum concentrations of neopterin, TNF-alpha and its soluble receptor sTNFRII p75 were studied in 40 female patients with SLE at various degrees of disease activity and in 10 matched for age and sex healthy controls by enzyme linked immunosorbent assay [ELISA]. SLE disease activity index [SLEDAI] score was used to assess disease activity. Thirty five, 30 and 28 of patients had LN, NPLE and vasculitis respectively as the main clinical manifestation. Renal biopsies were taken from 35 SLE patients who manifested with nephritis. Their pathology revealed that 7, 8, 9 and 10 had mesangial, membranous, focal and lastly diffuse LN. Of the 30 patients with NPLE, six patients were classified as having mild, 9 as having moderate, and 15 as having severe NPLE. Twenty eight of SLE patients manifested with vasculitis in the form of skin gangrene and ulcer or nail infarction or splinter hemorrhage. Serum levels of neopterin, TNF-alpha and sTNFRII of SLE patients were significantly higher than those of healthy controls [p<0.0001 for all]. While, TNF-alpha/ sTNFRII ratio was decreased significantly in SLE patients compared to healthy subjects [p<0.0001]. sTNFRII and TNF-alpha/sTNFRII were the only parameters that showed significantly higher or lower levels in SLE patients with mild activity classified according to SLEDAI score compared to normal subjects [p=0.0004, 0.0001]. Otherwise, the levels of neopterin, TNF-alpha and sTNFRII were significantly higher in either moderate or severe activity as scored by SLEDAI score compared to normal subjects [in moderate: for neopterin, TNF-alpha, sTNFRII p=0.0001, 0.03, 0.0001; for severe: p= 0.0001 for all respectively]. Patients with focal and diffuse LN had significantly increased serum levels of neopterin, TNF-alpha and sTNFRII, and a significantly higher SLEDAI score in comparison with those patients without LN [in focal: for neopterin, TNF-alpha, sTNFRII and score p=0.001, 0.01, 0.0001, 0.0002; for diffuse: p=0.0002,0.0004, 0.0001. 0.0001 respectively]. Patients with membranous LN had only increased sTNFRII level in comparison with those patients without LN [p=0.03]. Serum concentration of neopterin. TNF-alpha and sTNFRII were significantly elevated in both moderate, and severe NPLE and also patients' SLEDAI score as compared to those patients without NPLE [in moderate: neopterin, TNF-alpha, sTNFRII and score p= 0.008, 0.04, 0.001, 0.001 and in severe NPLE p =0.0001 for all respectively]. Serum concentrations of TNF-alpha and SLEDAI score were significantly higher in patients with severe NPLE than in mild NPLE [p=0.009, 0.004 respectively]. Serum concentration of neopterin was significantly elevated only in the mild NPLE [p=0.02] as compared to those patients without NPLE. Patients with vasculitis had significantly increased score and elevation of serum neopterin, TNF-alpha and sTNFRII compared to patients without vasculitis [p=0.02, 0.02, 0.0001, 0.009 respectively]. SLEDAI score were correlated positively with serum neopterin, TNF-alpha, sTNFRII and TNF-alpha/ sTNFRII levels [r=0.77, 0.75, 0.83, 0.35; p<0.0001 for the first 3 and 0.02 for the last respectively]. Also, serum neopterin levels showed significant positive correlation with serum TNF-alpha, sTNFRII and TNF-alpha/ sTNFRII levels [r=0.89, 0.94, 0.40 p<0.0001 for the first 2 and 0.008 for the last respectively] Measurement of serum sTNFRII is more better than TNF-alpha as a predictor of mild activity of SLE. However, serum neopterin is a useful parameter for detection of mild NPLE. Serum sTNFRII is a good parameter for better detection of all pathological types of lupus nephritis. Also, it was the one amongst other parameters measured that exhibited the higher significant elevation when comparing patients with different LN pathology. Even more, SLEDAI score showed the highest correlation with sTNFRII Lastly, TNF-alpha showed the highest significant elevation in patients with vasculitis

Serum neopterin level in childerin with acute rheumatic fever

Acute rheumatic fever [ARF] is a systemic inflammatory disease thought that immune activation may play an important role in the pathogenesis of the disease. The objective of. this study was to investigate serum concentration of marker of immune activation [Neopterin], in acute rheumatic fever patients. The study included 30, patients, 16 of them with acute rheumatic fever diagnosed according to updated J Jone's criteria and 14 childern of matched age, sex, socioeco-nomic st and er and didn't suffer sore-throat or other infection as control group. All studied childern subjected for detailed history analysis, clinical examination, ECG and echocardiography. Blood sambles were examined for CBC.CRP, Asot, and Neopterin level before and after treatment before discharge from the hospital.Analysis of the two groups data was performed using Student Test. Neopterin marker were analysed in both groups and the associated correlation between them and the laboratory data were evaluated. All the patients had elevated sedimentation rate [mean +/- SD: 76.3 +/- 27.2 mm/h.]. Increased ASOT [mean +/- SD: 345.8 +/- 137.6 Todd's]. Colour Echo- Doppler detected single mitral valve disease in 5 patients, mitral valve prolapse in one patient, mitral and aortic valve affection in 8 patients. Affection of mitral, aortic and tricuspid valves were detected in two patients Neoptrein was assessed in both patient and control group, the mean value was 11.5 +/- 8.8 nmol/1 during acute rheumatic fever and decreased to 7.5 +/- 2.3, nmol/1 during follow up before hospital -discharge. While it was 5.3 +1.8 nmol/1 in control group. Neopterin differ significantly than control group either during acute stage [P<.0001] or before hospital discharge [P <.05]. In conclusion serum neopterin is increased in acute rheumatic fever reflecting activation of the cellular immune system. Higher serum neopterin concentration are associated with development of combined aortic and mitral insufficiency. Neopterin may allow assessment of severity of cardiac involvement and may present markers by which immunosuppression can be judged.

Serum and synovial neopterin, a marker for rheumatoid arthritis activity

Rheumatoid arthritis [RA] is a chronic inflammatory disease of unknown etiology characterized by an erosive proliferative synovitis. Since the etiology of RA remains obscure, rheumatoid disease activity can only be evaluated by indirect laboratory measures. Despite the intensive efforts to make the clinical assessment more objective by applying numerical grades and indices, a relevant, reliable and reproducible method to quantitate rheumatoid activity is still needed. The pathogenesis of RA is complex involving many cells and cytokines. Neopterin, a pyrazino-pyrimidine derivative from gua-nosine triphosphate, was found to be an excellent biochemical marker for the invivo activation state of cell-mediated immunity. The aim of the present work was to study the monocyte/macrophage activation in RA patients by measuring neopterin concentration in serum and synovial fluid to test the efficacy of this new biochemical parameter in reflecting rheumatoid disease activity. 47 RA patients and 25 controls were included in this study Neopterin as well as other routine laboratory investigations were performed on the serum and synovial fluid [when applicable]. The results of this work showed that serum neopterin is significantly higher in RA patients than normal controls. Both serum and synovial fluid neopterin correlated strongly with the activity of the disease. Serum levels increased significantly as the disease becomes more active. If has been concluded that neopterin measurement can be used as a parameter of rheumatoid disease activity

Neopterin as an immunological marker

To compare between serum neopterin level in rheumatoid arthritis [RA] patients [active and nonactive], patients with some parasitic intestinal nematodes infestation and with normal controls. The patient groups were chosen to represent diseases in which cell mediated immunity is involved in the disease process. Also, to correlate changes in serum neopterin level with status of disease activity in patients with rheumatoid arthritis [RA] and with the load of some intestinal nematodes infestation. This study was done on the following groups. Group I included 20 inactive RA patients [8 males and l2females, 18-50 years old], Group II which included 20 active RA patients [7 males and 13 fema1es, 18-60 years old], Group III included 16 patients with enterobiasis [6 males and 10 females, 5-35 years old], group IV included 12 patients with ascariasis [8 males and 4 females, 4-30 years old], group V included 12 patients with ancylostomiasis [10 males and 2 females, 12-50 years old] and group VI which included 10 normal subjects [5 males and 5 females, 10-35 years old] with no evidence of any rheumatological disorder or parasitic infestation as a control group. RA disease activity was assessed according to the presence or absence of morning stiffness, pain, grip strength, and articular index. Group I, II and VI were subjected to full medical history and clinical examination, CBC and ESR, assay of rheumatoid factor [RF] by Rose-Waaler test, and X-ray on the affected joints and graded by modified Larsen et al. [1977] index .Group III, IV, V, and VI were subjected to full medical history and clinical examination, repeated stool analysis, perianal swab for suspected cases of pinworm infestation, and estimation of parasitic load. Quantitative measurement of serum neopterin was done for all persons included in the study. In RA patients both groups [I and II] were matched regarding age and disease duration. ESR and serum neopterin levels were higher in active disease group [highly significant difference]. In all RA patients there was a positive correlation between ESR and serum neopterin, and between ESR and serum RF levels. In group I, a positive correlation was found between ESR and serum neopterin levels. In group II, a positive correlation was found between age and disease duration, ESR and serum neopterin levels, ESR and serum RF levels, and between serum neopterin and serum RF levels. Also, serum neopterin was significantly elevated in groups III, IV, and V when compared to group VI. A highly significant difference was found on comparing serum neopterin level between patients with active RA and all parasitic patients, active RA and controls, inactive RA and controls, and all parasitic patients and controls [being higher in the former groups], while it was insignificant on comparing inactive RA and all parasitic patients. Furthermore, serum neopterin was significantly increased with increased parasitic load. Serum neopterin is significantly higher in sera of active RA patients and correlates with disease activity and also it is significantly higher in sera of patients with intestinal nematodes infestation and its level progressively rises with the increase in the parasitic load

relation between serum neopterin levels and insulin resistance in obese subjects

This study was conducted on 50 subjects, 30 obese healthy subjects with body mass index [BMI] of 31.897 +/- 2.806 Kg/m2 and 20 normal weight healthy subjects with BMI of 21.649 +/- 1.307 Kg/m2 served as a control group. Serum neopterin, fasting insulin, fasting blood glucose levels and homeostatic model assessment [HOMA] score were determined for all subjects. Compared with the control group, obese subjects had significantly higher fasting insulin concentration, fasting blood glucose levels, HOMA scores and serum neopterin levels. In obese subjects, serum neopterin levels had a significant positive correlation to BMI, fasting insulin, fasting blood glucose and to HOMA scores. In the control group, serum neopterin levels also had a significant positive correlation to BMI and HOMA scores. Z score showed that serum neopterin level was the most sensitive parameter that reflected the actual changes in obese subjects, followed by fasting insulin, then HOMA score and lastly fasting blood glucose