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Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in rheumatoid arthritis
- Source :
- Vosslamber, S, Raterman, H G, van der Pouw Kraan, T, Schreurs, M W J, von Blomberg, B M, Nurmohamed, M T, Lems, W F, Dijkmans, B A, Voskuyl, A E & Verweij, C L 2011, ' Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in rheumatoid arthritis. ', Annals of the Rheumatic Diseases, vol. 70, no. 6, pp. 1153-1159 . https://doi.org/10.1136/ard.2010.147199, Annals of the Rheumatic Diseases, 70(6), 1153-1159. BMJ Publishing Group
- Publication Year :
- 2011
-
Abstract
- ObjectiveDespite 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.MethodsGene 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.ResultsPharmacogenomic 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 (∆DASConclusionsA 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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Immunology
Severity of Illness Index
General Biochemistry, Genetics and Molecular Biology
Arthritis, Rheumatoid
Antibodies, Monoclonal, Murine-Derived
Rheumatology
Immunopathology
Internal medicine
medicine
Immunology and Allergy
Cluster Analysis
Humans
Aged
Oligonucleotide Array Sequence Analysis
Autoimmune disease
business.industry
Gene Expression Profiling
Middle Aged
medicine.disease
Prognosis
Connective tissue disease
Treatment Outcome
Gene Expression Regulation
Rheumatoid arthritis
Antirheumatic Agents
Significance analysis of microarrays
Interferon Type I
Rituximab
Female
business
Interferon type I
Biomarkers
medicine.drug
Subjects
Details
- ISSN :
- 14682060 and 00034967
- Volume :
- 70
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Annals of the rheumatic diseases
- Accession number :
- edsair.doi.dedup.....18cba6693687f87534b35035005a2453