SAT0666 ASSESSMENT OF INFLAMMATORY AND IMMUNE PATHWAYS IN RHEUMATOID ARTHRITIS PATIENTS USING BIOPRED KIT TO IDENTIFY CANDIDATE BIOMARKERS
Authors: Madah Mehdi, Eric Schordan, Matthieu Coq, Sami Ait Nazi, Hüseyin Firat, Christian Jorgensen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid Arthritis<b> (</b>RA) is a chronic, progressive, inflammatory autoimmune disease associated with articular, extra-articular and systemic effects leading to joint destruction. T cells, B cells and the orchestrated interaction of pro-inflammatory cytokines play key roles in the pathophysiology of RA. Better comprehension of interaction between cytokines and their signaling pathways are key for the development of new strategies with small molecules or biologicals. Today, new technologies allow the specific investigation of inflammatory pathways at mRNA level without extraction step directly from the blood. The BIOPRED panel, Disease activity specific gene enrichment studies in RA &amp; other autoimmune-inflammatory disorders would help pharmaceutical industry tailor target specific therapies and would help clinicians choose optimal &amp; personalized therapy for their patients. Therefore, we have identified active biological pathways in RA patients associated with different disease activity status. <h3>Objectives:</h3> By using Firalis' BIOPRED assay, a targeted gene sequencing panel including 2155 mRNAs from inflammatory and immune pathways, we aimed to identify active biological pathways in function to different disease activity status of RA and Healthy volunteer (HV) subjects. <h3>Methods:</h3> Paxgene samples of active RA patients with DAS28&gt;3.2 (n=178) and HV (n=25) are directly profiled without RNA extraction with BIOPRED assay and 2155 mRNA were quantified on HTG EdgeSeq platform, a combination of a nuclease protection assay &amp; next generation sequencing (NGS). Subjects are categorized into three groups; High disease activity (HDA) group with DAS28 &gt;5.1, Moderate disease activity (MDA) group with DAS28 between 3.2 and 5.1, and Healthy volunteer (HEV) group. <h3>Results:</h3> After transformation and normalization of the gene expression data, 22 mRNA genes are found to be significantly upregulated in RA (p-value &lt; 0.005, fold change &gt; 2) as compared to HV group. After ANOVA analysis on three groups as stated above, 351 mRNA targets are significantly regulated (p-value &lt;0.05). Pathway analysis based on protein-protein interaction from Biogrid, String and Intact database was used and score were generated based on fold change for 22 pathways to assess modification in HDA and MDA groups versus HV group. Various pathways including Jak/STAT pathway were shown to be significantly upregulated. <h3>Conclusion:</h3> Our results identify a list of mRNAs relevant to RA pathology and pathways that have the potential to be candidate biomarkers for disease activity, disease severity or as therapeutic targets. Moreover, BIOPRED panel accurately measures 2155 mRNA (Coefficient of Variation is less than 20% for more than 1100 mRNAs) from inflammatory and immune pathways and can be further used to study pathway analysis in autoimmune-inflammatory disorders such as RA. <h3>Disclosure of Interests:</h3> None declared