LAUSR

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.We identified pathways downstream to periodontitis onset that involved in RA progression with RNA-sequencing data.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 -log10(P) values larger than 1.3 were considered significant, and positive z-scores indicated up-regulation. The statistical software was Ingenuity Pathway Analysis (QIAGEN).Among all significantly enriched (-log10(P) > 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).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.[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-2019-216919Figure 1.Canonical pathway analysis on transcriptome of blood samples for patients with RA and gingival tissues for periodontitis.None declared