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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. Blood from healthy volunteers (n=4) was collected into sodium heparin tubes, and then untreated or treated with 294 pM recombinant human IFN-γ 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Mara Campbell 

PROVIDER: E-GEOD-78193 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.

Welcher Andrew A AA   Boedigheimer Michael M   Kivitz Alan J AJ   Amoura Zahir Z   Buyon Jill J   Rudinskaya Alla A   Latinis Kevin K   Chiu Kit K   Oliner Kelly S KS   Damore Michael A MA   Arnold Gregory E GE   Sohn Winnie W   Chirmule Narendra N   Goyal Lovely L   Banfield Christopher C   Chung James B JB  

Arthritis & rheumatology (Hoboken, N.J.) 20151001 10


<h4>Objective</h4>To assess the safety and immunologic impact of inhibiting interferon-γ (IFNγ) with AMG 811, a human IgG1 monoclonal antibody against IFNγ, in patients with systemic lupus erythematosus (SLE).<h4>Methods</h4>Twenty-six patients with mild-to-moderate, stable SLE were administered placebo or a single dose of AMG 811, ranging from 2 mg to 180 mg subcutaneously or 60 mg intravenously.<h4>Results</h4>Similar to results previously reported following inhibition of type I IFNs, treatmen  ...[more]

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