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| Status |
Public on Dec 30, 2013 |
| Title |
Effects of tocilizumab versus methotrexate therapy on gene expression profiles in the early rheumatoid arthrtis synovium |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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 patients’ 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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| Contributor(s) |
Ducreux J, Durez P, Toukap AN, Houssiau FA, Lauwerys BR |
| Citation(s) |
24449571, 25927832 |
| Submission date |
Apr 08, 2013 |
| Last update date |
Aug 09, 2019 |
| Contact name |
Bernard Robert Lauwerys |
| E-mail(s) |
Bernard.Lauwerys@uclouvain.be
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| Phone |
+3227645391
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| Organization name |
Université catholique de Louvain
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| Department |
Institut de Recherches Expérimentales et Cliniques
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| Lab |
Pôle de pathologies rhumatismales et systémiques
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| Street address |
Avenue Hippocrate 10
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| City |
Brussels |
| ZIP/Postal code |
1200 |
| Country |
Belgium |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (40)
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| GSM1116933 |
Synovial tissue prior to Tocilizumab therapy, repl 1 |
| GSM1116934 |
Synovial tissue after to Tocilizumab therapy, repl 1 |
| GSM1116935 |
Synovial tissue prior to Tocilizumab therapy, repl 2 |
| GSM1116936 |
Synovial tissue after to Tocilizumab therapy, repl 2 |
| GSM1116937 |
Synovial tissue prior to Tocilizumab therapy, repl 3 |
| GSM1116938 |
Synovial tissue after to Tocilizumab therapy, repl 3 |
| GSM1116939 |
Synovial tissue prior to Tocilizumab therapy, repl 4 |
| GSM1116940 |
Synovial tissue after to Tocilizumab therapy, repl 4 |
| GSM1116941 |
Synovial tissue prior to Tocilizumab therapy, repl 5 |
| GSM1116942 |
Synovial tissue after to Tocilizumab therapy, repl 5 |
| GSM1116943 |
Synovial tissue prior to Tocilizumab therapy, repl 6 |
| GSM1116944 |
Synovial tissue after to Tocilizumab therapy, repl 6 |
| GSM1116945 |
Synovial tissue prior to Tocilizumab therapy, repl 7 |
| GSM1116946 |
Synovial tissue after to Tocilizumab therapy, repl 7 |
| GSM1116947 |
Synovial tissue prior to Tocilizumab therapy, repl 8 |
| GSM1116948 |
Synovial tissue after to Tocilizumab therapy, repl 8 |
| GSM1116949 |
Synovial tissue prior to Tocilizumab therapy, repl 9 |
| GSM1116950 |
Synovial tissue after to Tocilizumab therapy, repl 9 |
| GSM1116951 |
Synovial tissue prior to Tocilizumab therapy, repl 10 |
| GSM1116952 |
Synovial tissue after to Tocilizumab therapy, repl 10 |
| GSM1116953 |
Synovial tissue prior to Tocilizumab therapy, repl 11 |
| GSM1116954 |
Synovial tissue after to Tocilizumab therapy, repl 11 |
| GSM1116955 |
Synovial tissue prior to Tocilizumab therapy, repl 12 |
| GSM1116956 |
Synovial tissue after to Tocilizumab therapy, repl 12 |
| GSM1116957 |
Synovial tissue prior to Methotrexate therapy, repl 1 |
| GSM1116958 |
Synovial tissue after to Methotrexate therapy, repl 1 |
| GSM1116959 |
Synovial tissue prior to Methotrexate therapy, repl 2 |
| GSM1116960 |
Synovial tissue after to Methotrexate therapy, repl 2 |
| GSM1116961 |
Synovial tissue prior to Methotrexate therapy, repl 3 |
| GSM1116962 |
Synovial tissue after to Methotrexate therapy, repl 3 |
| GSM1116963 |
Synovial tissue prior to Methotrexate therapy, repl 4 |
| GSM1116964 |
Synovial tissue after to Methotrexate therapy, repl 4 |
| GSM1116965 |
Synovial tissue prior to Methotrexate therapy, repl 5 |
| GSM1116966 |
Synovial tissue after to Methotrexate therapy, repl 5 |
| GSM1116967 |
Synovial tissue prior to Methotrexate therapy, repl 6 |
| GSM1116968 |
Synovial tissue after to Methotrexate therapy, repl 6 |
| GSM1116969 |
Synovial tissue prior to Methotrexate therapy, repl 7 |
| GSM1116970 |
Synovial tissue after to Methotrexate therapy, repl 7 |
| GSM1116971 |
Synovial tissue prior to Methotrexate therapy, repl 8 |
| GSM1116972 |
Synovial tissue after to Methotrexate therapy, repl 8 |
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| Relations |
| BioProject |
PRJNA196517 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45867_RAW.tar |
198.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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