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Blockade of interferon-γ normalizes IFN regulated gene expression in subjects with systemic lupus erythematosus (SLE)

ABSTRACT: Normal donor blood was incubated with or without IFN-g stimulation to establish an IFN-g gene signature. Systemic lupus erythematosus subjects were treated with placebo or AMG 811, a therapeutic anti-IFN--g antibody, and changes in the IFN--g signature in whole blood of these subjects was measured.

ORGANISM(S): Homo sapiens

PROVIDER: GSE78193 | GEO | 2016/02/24

SECONDARY ACCESSION(S): PRJNA312898

REPOSITORIES: GEO

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Blockade of interferon-Î³ normalizes IFN regulated gene expression in subjects with systemic lupus erythematosus (SLE)

Project description:Normal donor blood was incubated with or without IFN-g stimulation to establish an IFN-g gene signature. Systemic lupus erythematosus subjects were treated with placebo or AMG 811, a therapeutic anti-IFN--g antibody, and changes in the IFN--g signature in whole blood of these subjects was measured. Blood from healthy volunteers (n=4) was collected into sodium heparin tubes, and then untreated or treated with 294 pM recombinant human IFN-Î³ for 0, 24, or 48 hours with incubation at 37oC, 5 % CO2. The blood was then added to PAXgene tubes and processed for RNA purification. Twenty six subjects with stable, mild to moderate SLE were administered placebo or a single dose of AMG 811 ranging from 2 mg to 180 mg SC or 60 mg IV. Whole blood PAXgene tube samples were collected from all cohorts at baseline, day-1 (pre-dose), and at days 15, 56, and end of study (EOS) after treatment Arrays were hybridized in a Loop design.

2016-02-24 | E-GEOD-78193 | biostudies-arrayexpress

Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus [blood]

Project description:This is a phase I randomized, double-blind, placebo-controlled crossover study which sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein

2017-06-23 | GSE100430 | GEO

Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus [skin]

2017-06-23 | GSE100093 | GEO

Down-regulation of Interferon signature in systemic lupus erythematosus patients by active immunization with Interferon alpha-Kinoid

Project description:We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline. Anti-IFNalpha antibodies were detected in all IFN-K-immunized patients. Transcriptomic analysis separated patients at baseline into type I IFN signature-positive and -negative groups. IFN-K induced higher anti-IFNalpha titers in signature-positive than in signature-negative patients and, in signature-positive patients, reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNalpha antibody titers, and with baseline IFN score. IFN-K or placebo was administered at day 0, day 7, day 28 in all patients. Half the subjects received a fourth injection at day 84 (see treatment protocol)

2012-11-01 | E-GEOD-39088 | biostudies-arrayexpress

Gene expression in RNP autoantibody+ systemic lupus erythematosus (SLE) patient blood

Project description:The goal of this study was to characterize gene expression profiles in RNP autoantibody+ SLE versus healthy blood donors with a focus on select cytokines that may be important in B cell activation and differentiation, including BAFF, IL-21, and IL-33. We utilized Affymetrix microarrays to characterize the global program of gene expression in the SLE patients, and to identify differentially expressed genes in patients compared to healthy controls. We examined a cohort of 79 consecutive patients classified as anti-ribonuclear protein (anti-RNP)+ systemic lupus erythematosus (SLE). All patients provided RNA samples obtained after providing informed consent. There were 73 female and 6 male subjects. Disease duration ranged from 0 to 453 months with a median of 37.5 months. SLE Disease Activity Index (SLEDAI) ranged from 0 to 31 with a median of 6. mRNA from the blood of a SLE cohort (79 patients with some repeat visits for a total of 99 arrays) and 30 healthy volunteers (one array per volunteer) were analyzed.

2015-01-01 | E-GEOD-61635 | biostudies-arrayexpress

Gene expression in RNP autoantibody+ systemic lupus erythematosus (SLE) patient blood

2015-01-01 | GSE61635 | GEO

Transcription profiling of human peripheral blood lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus (SLE) patients reveals unique gene expression profiles compared to subsets isolated from healthy controls

Project description:Gene expression profile studies have identified an interferon signature in whole blood or mononuclear cell samples from patients with systemic lupus erythematosus. This study was designed to determine whether specific lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus patients demonstrated unique gene expression profiles compared to subsets isolated from healthy controls. Experiment Overall Design: The entire study included 67 samples. One CEL file was not available for SLE13_CD4

2008-04-05 | E-GEOD-10325 | biostudies-arrayexpress

IFN-α kinoid in systemic lupus erythematosus: Affymetrix Data

Project description:Objective: To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. Methods: Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering. Results: IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduce the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN- K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs. 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable. Conclusions: IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering. Trial registration number NCT02665364.

2021-10-08 | GSE185047 | GEO

Transcriptomic signature in patients with systemic lupus erythematosus (SLE) [T cells]

Project description:T cell abnormalities are well-known features of patients with systemic lupus erythematosus (SLE). The role of CD4 and CD8 T lymphocytes, however, remains poorly understood with data suggesting both protective and deleterious roles. This project aimed to identify a cell-specific transcriptional signature in patients with SLE that could be used as a prognostic disease marker. The overall objective is to correlate the clinical presentation with specific RNA signatures to determine if there are signatures that correlate with disease outcome

2021-02-11 | GSE97263 | GEO

Transcriptomic signature in patients with systemic lupus erythematosus (SLE) [CD8 T cells]

2021-02-11 | GSE97264 | GEO

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