التفاصيل البيبلوغرافية
| العنوان: |
THU0496 APPLICATION OF SYSTEMS BIOLOGY-BASED IN SILICO TOOLS TO OPTIMIZE TREATMENT STRATEGY IN STILL’S DISEASE |
| المؤلفون: |
Coma, M., Segú-Vergés, C., Kessel, C., Smeets, S., Foell, D., Aldea, A. |
| المصدر: |
Annals of the Rheumatic Diseases ; volume 79, issue Suppl 1, page 484-485 ; ISSN 0003-4967 1468-2060 |
| بيانات النشر: |
BMJ |
| سنة النشر: |
2020 |
| مصطلحات موضوعية: |
General Biochemistry, Genetics and Molecular Biology, Immunology, Immunology and Allergy, Rheumatology |
| الوصف: |
Background: Systemic Juvenile Idiopathic Arthritis (sJIA) and Adult Onset Still’s Disease (AOSD) are manifestations of an autoinflammatory disorder with complex pathophysiology and significant morbidity, together also termed Still’s disease. Objectives: To investigate the optimal treat-to-target strategy for Still’s disease by in silico models based on systems biology. Methods: Molecular characteristics of Still’s disease and data on biological inhibitors of interleukin (IL)-1 (anakinra, canakinumab), IL-6 (tocilizumab, sarilumab), glucocorticoids as well as conventional disease-modifying anti-rheumatic drugs (DMARDs, methotrexate) were used to construct in silico mechanisms of action (MoA) models by means of Therapeutic Performance Mapping System technology (TPMS). TPMS combines artificial neuronal networks (ANN), sampling-based methods and artificial intelligence. The models were validated with publicly available expression data from sJIA patients (Fig.1). Figure 1. Schematic TPMS approach used to evaluate the Still’s disease treatments efficacy and their MoA Results: Biologicals demonstrated more pathophysiology-directed efficiency than non-biological drugs. IL-1 blockade mainly acts on the innate immune system, while IL-6 signaling blockade has a weaker activity on the innate immunity and rather affects the adaptive immunity (Table 1). The MoA models showed that the IL-1β inhibitor canakinumab is more efficient than the IL-6 receptor inhibiting antibody tocilizumab in the autoinflammatory/systemic phases of Still’s disease. MoA models reproduced 67% of the information obtained from expression data (Fig.2). Table 1. Summary of ANN scores. A) Global Still’s disease evaluation. B) Immune system component. ANN scores mean the probability of the resulted relationship is true positive: +++ correspond to values >78% (p-value<0.05); ++ correspond to values > 59% (p-values<0.15) and; + correspond to values > 38% (p-value<0.25) A) Still’s disease molecular definition Biologics Non-biologics Anakinra ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1136/annrheumdis-2020-eular.4374 |
| الإتاحة: |
https://doi.org/10.1136/annrheumdis-2020-eular.4374Test |
| رقم الانضمام: |
edsbas.EA45EF8C |
| قاعدة البيانات: |
BASE |
