| Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in rheumatoid arthritis. | |
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MedLine Citation:
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PMID: 21444302 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: /st> Despite the fact that rituximab depletes B cells in all treated patients with RA, not all patients show a favourable clinical response. The goal of this study was to provide insight into pharmacological changes in peripheral blood that are associated with clinical response to rituximab. METHODS: /st> Gene expression profiling was performed on peripheral blood RNA of 13 patients with RA (test group) using Illumina HumanHT beadchip microarrays. An independent group of nine patients was used for validation using TaqMan quantitative PCR. Clinical responder status was determined after 6 months using change in 28-joint Disease Activity Score (ΔDAS28) and European League Against Rheumatism (EULAR) response criteria. Significance analysis of microarrays and ontology analysis were used for data analysis and interpretation. RESULTS: /st> Pharmacogenomic analyses demonstrated marked interindividual differences in the pharmacological responses at 3 and 6 months after start of treatment with rituximab. Interestingly, only differences in the regulation of type I interferon (IFN)-response genes after 3 months correlated with the ΔDAS28 response. Good responders (DAS>1.2; n=7) exhibited a selective increase in the expression of type I IFN-response genes, whereas this activity was unchanged or hardly changed in non-responders (DAS<1.2; n=6) (p=0.0040 at a cut-off of 1.1-fold induction). Similar results were obtained using EULAR response criteria. These results were validated in an independent cohort of nine patients (five non-responders and four responders, p=0.0317). CONCLUSIONS: /st> A good clinical response to rituximab in RA is associated with a selective drug-induced increase in type I IFN-response activity in patients with RA. This finding may provide insight in the biological mechanism underlying the therapeutic response to rituximab. |
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Authors:
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Saskia Vosslamber; Hennie G Raterman; Tineke C T M van der Pouw Kraan; Marco W J Schreurs; B Mary E von Blomberg; Michael T Nurmohamed; Willem F Lems; Ben A C Dijkmans; Alexandre E Voskuyl; Cornelis L Verweij |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-27 |
Journal Detail:
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Title: Annals of the rheumatic diseases Volume: - ISSN: 1468-2060 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372355 Medline TA: Ann Rheum Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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