Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro and in vivo, tryptophan degradation was found to be associated with T cell functional loss and tolerance induction. In systemic lupus erythematosus (SLE) besides the Th2-type cytokine interleukin-10, Th1-type cytokines including interferon-gamma (IFN-gamma) are expressed especially during exacerbation of the disease. IFN-gamma stimulates the enzyme indoleamine (2,3)-dioxygenase (IDO) converting tryptophan to the metabolite kynurenine which in macrophages is subsequently degraded to other, partly neurotoxic compounds like quinolinic acid, and finally to nicrotinamides. We measured kynurenine and tryptophan concentrations in the sera of 55 SLE patients. In these patients, the concentrations of tryptophan (median, interquartile range: 53.9, 45.7-64.1 microM) were lower (p < 0.0001), and the kynurenine concentrations (2.45, 1.75-3.40 microM) were increased (p < 0.0005) compared to healthy blood donors (70.0, 63.8-80.6; 1.80, 1.45-2.27 microM, respectively). Also the kynurenine per tryptophan quotients (K/T), which allow to estimate IDO activity, were significantly higher in patients than in normals (0.043, 0.033-0.062 vs. 0.027, 0.021-0.030; p < 0.0001), indicating enhanced IDO-induced tryptophan degradation in SLE. There was no significant relationship between tryptophan, kynurenine and the SLEDAI, and also the correlation of K/T with SLEDAI was rather weak (rs = 0.243, p < 0.05). Higher K/T was found in patients presenting with serositis (p = 0.01), decrease of complement (c3, c4; p < 0.01) and blood count change (anemia, leucopenia, lymphopenia; p = 0.032) than in patients without such disease manifestations. The significant correlation found between K/T and neopterin (rs = 0.808, p < 0.001), a marker of immune activation, points to a role of immune activation to be responsible for tryptophan degradation in SLE patients.
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PMID:Enhanced tryptophan degradation in systemic lupus erythematosus. 1083 18

Serum neopterin (SN), concentration of soluble (s) TNF-receptors (R) with molecular mass 55 kD and sIL-2R, C-reactive protein (CRP), Willebrand factor antigen (WF Ag) were measured in enzyme immunoassay (EIA) or radioimmunoassay (BRAHMS, Berlin, Germany) in 189 patients with autoimmune rheumatic diseases: 52 patients with systemic lupus erythematosus (SLE), 67 patients with rheumatoid arthritis (RA), 44 patients with polymyositis/dermatomyositis and 26 patients with Wegener granulomatosis. SN appeared elevated in autoimmune rheumatic diseases correlating with the disease activity and concentrations of sTNF R and sIL 2R. Assay for neopterin is clinically essential for examination of the immunopathological process activity, prediction of the outcomes, better knowledge about cytokine synthesis profile in autoimmune rheumatic diseases.
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PMID:[Neopterin: new immunological marker of autoimmune rheumatic disease]. 1101 25

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by flare-ups, the cause of which is unknown. According to new stress concepts, two "integrative single-case studies" have been conducted in order to gather evidence about whether daily stressful incidents and associated emotions interfere with the dynamics of urine cortisol and urine neopterin in SLE. Patients under study collected their urine at home, for a period of at least 50 days, on a daily basis, divided into day and night urine. Additionally, patients filled out questionnaires twice a day to determine their emotional state, life style and disease activity. Each week, patients were examined clinically and interviewed to identify the past week's stressors using the Incidents and Hassles Inventory (IHI, Brown and Harris). Statistical analysis of the serial data was performed using time-series analysis according to Box and Jenkins. In both "integrative single-case studies" we were able to demonstrate that stressful incidents predicted an increase in urine neopterin 36 hours (Case 1) to 60 hours (Case 2) later (p < 0.05). Additionally, in Case 1 the neopterin levels were highly associated with stress resulting from the weekly examinations and interviews. Furthermore, in Case 2 it turned out that depending on their predictability stressful incidents were preceded by a decrease in urine cortisol 12 hours earlier or were followed by a decrease in urine cortisol 36 hours later. And finally, emotional irritation was highly correlated with the course of urine-neopterin. In Case 2 irritation led to an increase in urine neopterin 84 hours later. There were no clinical signs of SLE during both prospective studies. In conclusion, our results validate the idea of "integrative single-case studies" as a new "bio-psycho-social" approach in psychoneuroimmunology. Further studies with SLE patients as well as with healthy probands will be necessary in order to both strengthen and generalize these results.
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PMID:[The influence of daily psychosocial stressors and associated emotions on the dynamic course of urine cortisol and urine neopterin in systemic lupus erythematosus: Experience taken from two "integrative single-case studies"]. 1159 54

The objective of this study was to assess the utility of measurement of thrombomodulin, antinucleosome antibodies, sVCAM-1, sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R in patients with systemic lupus erythematosus (SLE) and to compare them with traditional markers of SLE activity (anti-dsDNA antibodies, C3, C4) and the ECLAM index of disease activity. The measurement was performed over a 6-month period at three consecutive time points after 3 months in each of the 52 patients with SLE. Anti-dsDNA antibodies, thrombomodulin, antinucleosome antibodies, sVCAM-1m sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R were tested by ELISA technique, while C3, C4 components of complement were tested by nephelometry. Fas ligand and IL-10 did not correlate with the ECLAM index. The rest of the markers showed significant correlation with the disease activity index. Thrombomodulin and anti-dsDNA antibodies reflect in the best way the changing trend in disease activity. Antinucleosome antibodies seem to be a promising marker useful in early diagnosis. Soluble VCAM-1, sICAM-1, neopterin and sIL-2R are interesting molecules with a role in disease pathogenesis, but their practical utility is limited.
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PMID:Clinical utility of selected disease activity markers in patients with systemic lupus erythematosus. 1164 15

This study investigated the complex biochemical responses to personally meaningful everyday stressors in a patient with systemic lupus erythematosus (SLE). For this purpose, a 52 year-old woman with SLE collected her entire urine for 56 days on a 12-h basis for the determination of cortisol as well as neopterin, a cellular immune parameter. Additionally, using questionnaires, daily notes and interviews, extensive psychosocial and psychological time-series data were collected every 12 h. Cross-correlational analyses of the resulting time-series revealed that stressful incidents were associated with cyclic fluctuations in both urine cortisol and urine neopterin. Specifically, whenever the patient anticipated a moderately stressful incident, urine cortisol initially increased 24 h before the incident and then decreased 12 h before the incident. Moderate stressors not anticipated by the patient were associated with an initial increase 24 h following the incident and then with a decrease after a total of 36 h. Moreover, stressors having to do with the patient's extramarital relationship were followed initially by a decrease in urine neopterin after 36 h and then by an increase after a total of 60 h. Our findings indicate that when investigating the relationship between psychosocial stressors and biochemical activity in SLE, appropriate consideration of the data's dynamic nature may be necessary to avoid flawed conclusions.
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PMID:Daily psychosocial stressors and cyclic response patterns in urine cortisol and neopterin in a patient with systemic lupus erythematosus. 1257 8

Neopterin (Neo) and 7,8-dihydroneopterin (H(2)Neo) are produced by human monocyte-derived macrophages upon stimulation with IFN-gamma. Increased amounts of Neo and H(2)Neo in human body fluids are found in many disorders, including viral infections and autoimmune diseases. Recent data suggest that neopterin derivatives may exhibit distinct biochemical functions activating redox-sensitive transcription factors and inducing apoptosis in various cell lines. In this study we investigated the effect of H(2)Neo on human peripheral blood T cells (PBT) from healthy blood donors in comparison with PBT isolated from patients with systemic lupus erythematosus (SLE). H(2)Neo induced apoptosis in healthy PBT in a concentration-dependent manner. In short time culture, a significantly lower ability of PBT isolated from patients with SLE to undergo apoptosis in response to H(2)Neo compared to healthy controls was detected. Our results suggest a possible role of the neopterin derivative H(2)Neo in T cell apoptosis mediated by stimulated monocytes/macrophages.
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PMID:Induction of apoptosis in human blood T cells by 7,8-dihydroneopterin: the difference between healthy controls and patients with systemic lupus erythematosus. 1280 28

Neopterin plays an important role in the malignant disease diagnostics. However, the methods employed in neopterin determination are generally difficult and/or time consuming. The aim of this work was to standardize a practical method to quantify neopterin using high-performance liquid chromatography-ultraviolet (HPLC-UV) and quantify it in patients with systemic lupus erythematosus (SLE). Urine was collected from healthy subjects (n= 49), patients with inactive (n= 15), active (n= 28), and highly active SLE (n= 6). The HPLC was performed using two coupled reverse-phase columns eluted with 150 mM sodium phosphate, pH 4.0, under a flow rate of 0.8 ml/min, with UV detector set at 353 nm and 100-fold diluted urines. The inter- and intra-assay studies presented an imprecision of 12.5% and 12.9% for quality controls of 3.94 and 1.1 micromol/ml, respectively. Recovery from 79.5% to 82% was observed throughout the assay's linear range. Subjects with active (874.2 +/- 165.38 micromol/mol creatinin) and highly active SLE (1753.8 +/- 453.9 micromol/mol creatinin) showed three- and sixfold increased neopterin levels, respectively, compared to subjects with inactive SLE (314.3 +/- 121.3 micromol/mol creatinin) and healthy subjects (294.6 +/- 178.6 micromol/mol creatinin) (P< 0.05). Briefly, the proposed method was precise, specific, and reproducible, not invasive and allows the urinary neopterin quantification only with UV detection.
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PMID:Urinary neopterin quantification by reverse-phase high-performance liquid chromatography with ultraviolet detection. 1641 60

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.
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PMID:[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes]. 1534 34

Increased lymphocyte apoptosis and defects in macrophage removal of apoptotic cells have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the relationship between peripheral lymphocyte apoptosis, macrophage function as determined by the serum levels of neopterin and interferon-gamma (IFN-gamma), and SLE disease activity. Peripheral apoptotic lymphocytes (AL) were detected by annexin V-fluorescein isothiocyanate (FITC) staining and flow cytometry. Serum levels of neopterin and IFN-gamma were measured by enzyme-linked immunosorbent assay (ELISA). SLE disease activity was determined using the systemic lupus activity measure (SLAM) and the serum titer of anti-dsDNA antibodies. The percentage of AL in the peripheral blood of active SLE patients was significantly higher (13.07+/-7.39%, n=30) than that of the inactive SLE patients (4.08+/-3.55%, n=8, p<0.01) and normal controls (5.13+/-3.37%, n=11, p<0.01). Serum levels of neopterin in active SLE patients were significantly higher (1.39+/-1.10 microg/dl, n=22) than in controls (0.26+/-0.19 microg/dl, n=20, p<0.01). Serum levels of IFN-gamma in active SLE patients were elevated (58.97+/-34.52 ng/l, n=15) when compared with controls (28.06+/-2.35 ng/l, n=16, p<0.05). The percentage of AL correlated significantly with serum levels of neopterin (r=0.446, p<0.05, n=22) and SLAM score (r=0.533, p<0.001, n=38), but not with the serum levels of IFN-gamma. The SLAM score also correlated with the serum levels of neopterin (r=0.485, p<0.05, n=22), but not with those of IFN-gamma. Our study supported the hypothesis that increased lymphocyte apoptosis has a pathogenic role in SLE. The increased levels of serum neopterin may suggest an attempt of the patients' macrophage system to remove the apoptotic cell excess. Since serum levels of neopterin correlated with the overall lupus disease activity, they may be regarded as an index of SLE disease activity.
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PMID:Lymphocyte apoptosis and macrophage function: correlation with disease activity in systemic lupus erythematosus. 1581 11

Neopterin is a low-molecular mass substance synthesized from guanosine triphosphate (GTP) in monocytes/macrophages due to IFNgamma stimulation. The cellular immune system is involved in or affected by the disease process in various conditions such as viral infections (AIDS), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosis, Crohn's disease), malignancy and monitoring after solid organ transplants. Similar to procalcitonin, neopterin determination can assist in the differential diagnosis between viral and bacterial infection and as an indicator for impending septic complications (MODS vs. sepsis). Because of fact that reduced glamerular filtration rate neopterin accumulates in the blood, neopterin determination in multiorgan failure or sepsis patients are limited. The aim of this study was to evaluate the usefulness of neopterin in clinical diagnostics.
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PMID:[Role of neopterin in clinical diagnostics]. 1646 8


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