POS0402 IDENTIFYING MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN RHEUMATOID ARTHRITIS AND PERIODONTITIS USING IN SILICO ANALYSIS OF CANONICAL PATHWAYS
Authors: K. S. K. Ma, L. T. Wang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Periodontal pathogens such as Porphyromonas gingivalis (P.g. ) has been proposed too involve in rheumatoid arthritis (RA) progression via citrullinating and producing exogenously citrullinated human and bacterial epitopes. Objectives: We identified pathways downstream to periodontitis onset that involved in RA progression with RNA-sequencing data. Methods: Canonical pathway analysis was conducted by comparing mRNA expression data from whole-transcriptome expression profiling using z-score and p-value visualization to identify underlying mechanisms among patients with RA (n=7) and periodontitis (n=9). Collected biopsies included human blood samples for RA and human gingival tissues for periodontitis. RNA-seq data with -log 10 (P) values larger than 1.3 were considered significant, and positive z-scores indicated up-regulation. The statistical software was Ingenuity Pathway Analysis (QIAGEN). Results: Among all significantly enriched (-log10(P) &gt; 1.3) periodontitis-associated pathways underlying RA progression identified from the recruited cases, the production of nitric oxide and reactive oxygen species in macrophages, B cell receptor signaling, osteoarthritis pathway, HOTAIR regulatory pathway, IL-8 signaling, LPS/IL-1 mediated inhibition of RXR function, leukocyte extravasation signaling, and neuroinflammation signaling pathway, were up-regulated in RA patients and patients with periodontitis, when compared with patients without either disease. The z-scores of production of nitric oxide and reactive oxygen species in macrophages were 2.45 for RA (-log10(P) = 1.41), 3.89 for periodontitis (-log10(P) = 4.25); the z-scores of B cell receptor signaling were 2.44 for RA (-log10(P) = 1.93), 2.65 for periodontitis (-log10(P) = 6.97); the z-scores of osteoarthritis pathway were 1.89 for RA (-log10(P) = 3.28), 2.33 for periodontitis (-log10(P) = 4.31); the z-scores of HOTAIR regulatory pathway were 1.63 for RA (-log10(P) = 1.71), 3.40 for periodontitis (-log10(P) = 3.68); the z-scores of IL-8 signaling were 1.34 for RA (-log10(P) = 1.30), 4.43 for periodontitis (-log10(P) = 6.05); the z-scores of LPS/IL-1 mediated inhibition of RXR function were 1.33 for RA (-log10(P) = 2.00), 1.27 for periodontitis (-log10(P) = 3.44); and the z-scores of leukocyte extravasation signaling were 1.13 for RA (-log10(P) = 1.80), 3.68 for periodontitis (-log10(P) = 18.14). Conclusion: Our findings suggest that infection-driven activation of macrophages and B cells is involved in RA pathogenesis. This occurs primarily through upregulating cellular activities involving iNOS-presenting macrophages and B cell receptor signaling, which may be associated with the pathogenesis of P.g. -triggered RA. References: [1]Jenning M, Marklein B, Ytterberg J, et al. Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Ann Rheum Dis 2020;79:1194–202.doi:10.1136/annrheumdis-2019-216919 Figure 1. Canonical pathway analysis on transcriptome of blood samples for patients with RA and gingival tissues for periodontitis. Disclosure of Interests: None declared