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Combination of peripheral blood gene expression profiles and clinical parameters predicts response for tocilizumab (anti-IL6) treatment in rheumatoid arthritis

ABSTRACT: We used microarrays to identify markers predicting responder status in tocilizumab treatment in rheumatoid arthritis in 13 patients at week 0 and week 4 of treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE25160 | GEO | 2011/03/01

SECONDARY ACCESSION(S): PRJNA134351

REPOSITORIES: GEO

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Combination of peripheral blood gene expression profiles and clinical parameters predicts response for tocilizumab (anti-IL6) treatment in rheumatoid arthritis

Project description:We used microarrays to identify markers predicting responder status in tocilizumab treatment in rheumatoid arthritis in 13 patients at week 0 and week 4 of treatment. Peripheral blood samples were obtained at week 0 and week 4 of tocilizumab treatment and global gene expression profiling identified markers of responder status.

2011-03-01 | E-GEOD-25160 | biostudies-arrayexpress

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Effects of tocilizumab versus methotrexate therapy on gene expression profiles in the early rheumatoid arthrtis synovium

Project description:Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines & chemokines (e.g. IL-6, IL-7, IL-22, CCL8, CCL11, CCL13, CCL19, CCL20), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared to Methotrexate, Rituximab, or Adalimumab therapies. By opposition to the effects of Adalimumab, Tocilizumab therapy does not induce a decreased expression of genes involved in cell proliferation. Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. SDAI remission criteria were computed prospectively before, 3 months and 6 months after administration of the drugs and patientsM-bM-^@M-^Y responses were defined according to their SDAI remission status at 6 months. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 arrays.

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Effects of tocilizumab versus methotrexate therapy on gene expression profiles in the early rheumatoid arthrtis synovium

2013-12-30 | GSE45867 | GEO

Short Term Immune Response to IL6 inhibition (Tocilizumab)

Project description:we examined the effects of IL6 inhibition treatment on biologic molecular pathways in a 59 year old patient well diagnosed with RA with inadequate response to DMARD thus treated with tocilizumab. To assess the immunological outcome we used quantitative proteome analysis to evaluate changes in the proteome profile of different biologic pathways in leukocyte cell populations important to RA pathogenesis isolated by positive enrichment of CD14, CD4, CD8, CD19, and CD56.

2016-01-05 | PXD002686 | Pride

Transcriptome change after tocilizumab therapy in rheumatoid arthritis patients

Project description:We compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes.

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Gene Expression Analysis in Peripheral Blood of Patients with Rheumatoid Arthritis

Project description:Peripheral blood cells in patients with rheumatoid arthritis before/after IL-6 inhibition The obtained conclusions on the change of each gene expression level before and after MRA medication were as follows. (1) In the case of IL-6, the specific time profile that the expression level dropped at day 21 and increased to some extent at day 42 was observed in 2 of 18 subjects. In other subjects, quite small change or small increase after day 7 was observed. (2) In the case of IL-6R as well as in IL-6, the specific time profile that the expression level dropped at day 21 and increased to some extent at day 42 was observed in 1 of 18 subjects. In other subjects, slow and small increase was observed in 6 of 18. (3) The ratio of mRNA expression level of membrane and soluble type of IL-6R showed marginal difference after tocilizumab treatment, (4) The distinct change of expression level of cytochrome P450 mRNA after tocilizumab treatment was hardly observed in most patients. The measurement of expression level of several genes shown below in peripheral blood of human subjects (18 patients with rheumatic disease) before and after tocilizumab medication using DNA microarray (Hitachi human oligo chip) was conducted in this test, 1) Interleukin 6 (IL-6), membrane IL-6 receptor (IL-6R) and soluble type of the IL-6R, 2) several cytochrome P450 as follows: CYP3A4, CYP2D6, CYP2C9, CYP2C19. Number of human subjects was 18 and peripheral blood samples drawn at 4 time points: day 0 (the first Omeprazole administration was done), day 7 (Tocilizumab administration was done), day 21 and day 42 for each subject were analyzed. On day 0 and day 7, the blood sampling was done before drug administration.

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