NDLI: Modular analysis of peripheral blood gene expression in rheumatoid arthritis captures reproducible gene expression changes in tumor necrosis factor responders.

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Modular analysis of peripheral blood gene expression in rheumatoid arthritis captures reproducible gene expression changes in tumor necrosis factor responders.

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Year: 2015 Volume: 67 Issue: 1

Year: 2014 Volume: 66

Modular analysis of peripheral blood gene expression in rheumatoid arthritis captures reproducible gene expression changes in tumor necrosis factor responders.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Oswald, Michaela Curran, Mark E. Lamberth, Sarah L. Townsend, Robert M. Hamilton, Jennifer D. Chernoff, David N. Carulli, John Townsend, Michael J. Weinblatt, Michael E. Kern, Marlena Pond, Cassandra M. Lee, Annette Gregersen, Peter K.
Description	Author Affiliation: Oswald M ( Feinstein Institute for Medical Research, Manhasset, New York.)
Abstract	OBJECTIVE: To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). METHODS: Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. RESULTS: Good and moderate responders according to the European League Against Rheumatism criteria exhibited highly significant and consistent changes in multiple gene expression modules after 14 weeks of therapy, as demonstrated by hypergeometric analysis. Strikingly, nonresponders exhibited very little change in any modules, despite exposure to TNF blockade. These patterns of change were highly consistent across all 3 cohorts, indicating that immunologic changes after TNF treatment are specific to the combination of both drug exposure and responder status. In contrast, modular patterns of gene expression did not exhibit consistent differences between responders and nonresponders at baseline in the 3 study cohorts. CONCLUSION: These data provide evidence that using gene expression modules related to inflammatory disease may provide a valuable method for objective monitoring of the response of RA patients who are treated with TNF inhibitors.
File Format	HTM / HTML
ISSN	23265191
e-ISSN	23265205
DOI	10.1002/art.38947
Journal	Arthritis & Rheumatology
Issue Number	2
Volume Number	67
Language	English
Publisher	Wiley
Publisher Date	2015-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Rheumatology Antirheumatic Agents Pharmacology Therapeutic Use Arthritis, Rheumatoid Drug Therapy Genetics Gene Expression Regulation Drug Effects Blood Tumor Necrosis Factor-alpha Antagonists & Inhibitors Adalimumab Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Cohort Studies Dose-response Relationship, Drug Etanercept Immunoglobulin G Infliximab Predictive Value Of Tests Prospective Studies Receptors, Tumor Necrosis Factor Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology

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