Artikel
Whole transcriptome analysis confirms HLA-DRB1 as a strongly regulated gene in systemic juvenile idiopathic arthritis in remission
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Autoren
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Boris Hügle
- Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen
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Anastasia Wiener
- Universitätsklinikum der RWTH Aachen, Klinik für Kinder- und Jugendmedizin, Aachen
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Bernd Denecke
- Interdisziplinäres Zentrum für Klinische Forschung, Aachen
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Ivan Costa-Filho
- IZKF Computational Biology Research Group RWTH Aachen, Aachen
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Klaus Tenbrock
- Universitätsklinikum der RWTH Aachen, Klinik für Kinder- und Jugendmedizin, Aachen
| Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease characterized by arthritis and severe systemic inflammation. Treatment with interleukin(IL)-1 antagonists has shown to be effective when introduced early in the disease. The objective of this study was a longitudinal whole transcriptome analysis of children with (sJIA during the early phase of treatment with IL-1 antagonists to identify targets that predict response to therapy.
Methods: From the database of the German AIDnet database, patients with sJIA and active systemic disease treated with anakinra and subsequent remission were identified. Clinical data was obtained by retrospective chart review. Whole blood was drawn during active disease before initiation of anakinra and after achievement of remission. RNA was extracted and subjected to Affymetrix HTA 2.0 Arrays followed by intraindividual analysis of regulated genes in each patient and combined analysis of the genes in all the patients including GO analysis of differentially expressed genes.
Results: Six children with sJIA with active systemic disease were included in the study. Using a p-value of <0.01 and a fold change of 2 or greater, 742 genes were identified of which most were associated with immune mediated processes. Using a fold change of higher than 3 as a more stringent criterium, still more than 100 genes remained. Besides S100A8, our analysis revealed HLADRB1 as the most strongly upregulated gene in remission compared to active disease (FC 6.8). This gene has been recently identified as a risk factor in an association study of 982 children with sJIA and 8,010 healthy control subjects. Moreover an upregulation of CD177 a molecule engaged in neutrophil activation and transmigration was also found in these patients, which has not been described in previous studies.
Conclusion: Our study identifies new genes and confirms the strong up-regulation of HLA-DRB1 in patients with sJIA in remission on treatment with IL-1 antagonists. Additionally CD177 was observed as an additional player engaged in sJIA. Studies with larger patient cohorts are necessary to confirm these results.
