Linked Life Data

20948567

Source:http://linkedlifedata.com/resource/pubmed/id/20948567

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-10-15
pubmed:abstractText
To identify potential pharmacodynamic biomarkers to guide dose selection in clinical trials using anti-interferon-alpha (IFN-?) monoclonal antibody (mAb) therapy for systemic lupus erythematosus (SLE), we used an Affymetrix human genome array platform and identified 110 IFN-?/?-inducible transcripts significantly upregulated in whole blood (WB) of 41 SLE patients. The overexpression of these genes was confirmed prospectively in 54 additional SLE patients and allowed for the categorization of the SLE patients into groups of high, moderate, and weak overexpressers of IFN-?/?-inducible genes. This approach could potentially allow for an accurate assessment of drug target neutralization in early trials of anti-IFN-? mAb therapy for SLE. Furthermore, ex vivo stimulation of healthy donor peripheral blood mononuclear cells with SLE patient serum and subsequent neutralization with anti-IFN-? mAb or anti-IFN-? receptor mAb showed that anti-IFN-? mAb has comparable effects of neutralizing the overexpression of type I IFN-inducible genes as that of anti-IFNAR mAb. These results suggest that IFN-?, and not other members of type I IFN family in SLE patients, is mainly responsible for the induction of type I IFN-inducible genes in WB of SLE patients. Taken together, these data strengthen the view of IFN-? as a therapeutic target for SLE.
pubmed:language
eng
pubmed:journal
pubmed:status
PubMed-not-MEDLINE
pubmed:issn
1757-4242
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2009
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:year
2009
pubmed:articleTitle
Development of Potential Pharmacodynamic and Diagnostic Markers for Anti-IFN-? Monoclonal Antibody Trials in Systemic Lupus Erythematosus.
pubmed:affiliation
MedImmune, LLC., One MedImmune Way, Gaithersburg, MD 20878, USA.
pubmed:publicationType
Journal Article