Rheumatology Advance Access originally published online on April 3, 2008
Rheumatology 2008 47(6):780-788; doi:10.1093/rheumatology/ken083
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Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-
monoclonal antibody, infliximab
1Division of Rheumatology/Clinical Immunology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, Saitama, 2Japan Genome Solutions, Inc., Tokyo and 3Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Tokyo, Japan.
Correspondence to: T. Takeuchi, Division of Rheumatology/Clinical Immunology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, 1981 Tsujido-machi, Kamoda, Kawagoe-shi, Saitama 350-8550, Japan. E-mail: tsutake{at}saitama-med.ac.jp
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Abstract |
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Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-
inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.
Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks.
Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.
Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.
KEY WORDS: Rheumatoid arthritis, Oligonucleotide array sequence analysis, Biological products, Infliximab, Tumour necrosis factor, Interferons, Messenger ribonucleic acid, Reverse transcriptase-polymerase chain reaction
Submitted 13 April 2007;
revised version accepted 4 February 2008.
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