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Scatter plots for 10 individual patients showing a consistent response over 24 months. Five good and 5 poor responders were randomly selected from each group with macroarray data at baseline, 6 months, and 24 months. The first 3 columns show patients with a good treatment response, and the last 3 columns are patients with a poor treatment response.

Columns 1 and 4 compare responses at baseline and 6 months; columns 2 and 5 compare responses at 6 and 24 months; and columns 3 and 6 compare responses at baseline at 24 months.

Note the consistency of response for all time points and that the molecular response is consistent regardless of whether treatment response is good or poor. We thank Dr. Joerg Schlaak University of Essen, Germany and his colleagues for extensive and thoughtful assistance during the development of the macroarray assay.

The NIH had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Without charge, Biogen Idec tested serum from the study subjects for neutralizing antibodies at 6 months and provided the data to the investigators. Biogen Idec had no role in study design, data analysis, decision to publish, or preparation of the manuscript. National Center for Biotechnology Information , U.

PLoS One. Published online May Richard A. Ransohoff 1 , 2. Sandhya Rani. Richard M. Steven Jacobson, Editor. Author information Article notes Copyright and License information Disclaimer. Received Dec 30; Accepted Mar Copyright Rudick et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. This article has been cited by other articles in PMC. Figure S2: Scatter plots for 10 individual patients showing a consistent response over 24 months. Table S1: DOC. Genes analyzed by macroarray The cDNA macroarray analysis was performed as previously described [22] , [23].

Open in a separate window. Figure 1. Correlations between induction ratios IRs for two patients at the initial baseline and 6-month injections. Figure 2. Scatter plots showing correlations between induction ratios between 3 time points over 24 months. Figure 3. Number of genes with an exaggerated response in poor responders at the initial A and 6-month injection B.

Figure 4. The magnitude of the exaggerated response for good and poor responder groups at the initial A and the 6-month B injection. EPS Click here for additional data file. Figure S2 Scatter plots for 10 individual patients showing a consistent response over 24 months. Acknowledgments We thank Dr.

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J Neurovirol. Background: Fibrosis of the intestine is a common and poorly understood complication of Crohn's disease CD characterized by excessive deposition of extracellular matrix and accompanied by narrowing and obstruction of the gut lumen. Defining the molecular characteristics of this fibrotic disorder is a vital step in the development of specific prediction, prevention, and treatment strategies. Previous epigenetic studies indicate that alterations in DNA methylation could explain the mechanism by which mesenchymal cells adopt the requisite pro-fibrotic phenotype that promotes fibrosis progression.

However, to date, genome-wide analysis of the DNA methylome of any type of human fibrosis is lacking. We employed an unbiased approach using deep sequencing to define the DNA methylome and transcriptome of purified fibrotic human intestinal fibroblasts HIF from the colons of patients with fibrostenotic CD. Results: When compared with normal fibroblasts, we found that the majority of differential DNA methylation was within introns and intergenic regions and not associated with CpG islands.