Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

Lim, K L; Jones, Adrian; Brown, N. S.; Powell, R J

doi:10.1136/ard.52.6.429

Cited by 32 publications

(16 citation statements)

References 30 publications

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“…13 IFN-γ or molecules that are upregulated by IFN-γ, such as IFN-γ-inducible protein 10 (CXCL-10), human leukocyte antigen (HLA) class II and neopterin, are present at increased levels in patients with SLE, including those with LN, and have been associated with disease activity and flares. [14][15][16][17][18][19][20] AMG 811 is a fully human (IgG1) anti-IFN-γ antibody. In patients with mild-to-moderate SLE, single doses of AMG 811 normalised IFN-regulated gene expression, led to dose-related reductions in serum CXCL-10, and were well tolerated.…”

Section: Introductionmentioning

confidence: 99%

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis

et al. 2017

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ObjectiveTo evaluate safety, pharmacokinetics and pharmacodynamics of anti-interferon (IFN)-γ monoclonal antibody AMG 811 in subjects with SLE without or with lupus nephritis (LN).MethodsIn this phase Ib, randomised, multiple-dose escalation study (NCT00818948), subjects without LN were randomised to subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks for three total doses. Outcomes included incidence of adverse events (AEs); pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte chemotactic protein-1); changes in gene transcript profiles and clinical parameters (Safety of Estrogen in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores, proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 complement, C4 complement).ResultsFifty-six subjects enrolled (28 SLE without LN; 28 with LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE subjects without and with LN, respectively. Most subjects reported an AE; no meaningful imbalances were observed between AMG 811 and placebo. Pharmacokinetic profiles were similar and mostly dose-proportional in subjects without or with LN. AMG 811 treatment reduced CXCL-10 protein levels and blood-based RNA IFN-γ Blockade Signature compared with placebo. Reductions were less pronounced and not sustained in subjects with LN, even at the highest dose tested, compared with subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4 complement levels, or anti-dsDNA antibodies was observed.ConclusionAMG 811 demonstrated favourable pharmacokinetics and acceptable safety profile but no evidence of clinical impact. IFN-γ-associated biomarkers decreased with AMG 811; effects were less pronounced and not sustained in LN subjects.Trial registration numberNCT00818948; results.

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Section: Introductionmentioning

confidence: 99%

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis

et al. 2017

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“…Neopterin measurement can be applied as an additional criterion to discriminate rheumatoid arthritis from osteoarthritis, because in the latter case, neopterin concentrations are usually within the normal range (69). In patients with systemic lupus erythematosus (SLE), extremdy high neopterin concentrations are found in the active state of the disease (71,72 ). The correlation between serum neopterin concentrations and disease acti\'in' was demonstrated in a ll1ultiyariate ,1l1,1Ini<' .…”

Section: S Ecpterin In Autoimmune Diseasesmentioning

confidence: 99%

The Importance of Neopterin as a Laboratory Diagnostic Marker of Immune Activation

et al. 1999

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SummaryNeopterin is produced and secreted in large amounts by interferon-g stimulated human monocytes/ macrophages. Neopterin measurement in urine and semm provides a usefi.ll possibility to estimate the dcgree of ccllular (Thl-type) immune activation, which is directed against viral infections, intracellular bacteria, and certain parasites. Also in malignancy, autoimmw1e diseases and allograft rejection episodes neopterin sensitively reflects the extent of cellular immune activation. Determination of neoptcrin concentrations can be conveniently performed by immunoassay like ELISA or RIA, and HPLC. The major diagnostic applications of neopterin monitoring are: surveillancc of the immw1e status of organ recipients, therapy control and prognosis of diseasc progression in tumor diseascs and HIV infections and also detection of unknown infections in e.g. blood banks. High neopterin levels are strongly associated with oxidative stress, opening an additional application field of ncopterin monitoring to estimate the extent of tissue damagc in the course of immune activation.

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“…Все они свидетельствуют о значительном повышении его концентрации у больных СКВ по сравнению со здоровыми донорами и положитель-ной корреляции с активностью болезни [37][38][39][40], что сов-О р и г и н а л ь н ы е и с с л е д о в а н и я…”

Section: Discussionunclassified

Role of Inflammation Markers in Development of Atherosclerosis and Its Compications in Patients With Systemic Lupus Erythematosus

Popkova¹,

Panafidina²,

Новикова³

et al. 2014

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Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

Abstract: Objectives-To investigate urine neop-

Cited by 32 publications

References 30 publications

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis

The Importance of Neopterin as a Laboratory Diagnostic Marker of Immune Activation

Role of Inflammation Markers in Development of Atherosclerosis and Its Compications in Patients With Systemic Lupus Erythematosus

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