P011 The role of cellular metabolism in rheumatoid and psoriatic arthritis

Abstract

Career situation of first and presenting authorPost-doctoral fellow.IntroductionRheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) share common features such as synovial hyperplasia, cartilage degradation and subchondral bone remodelling, however, there are distinct pathologic differences, which aid their diagnosis, and may account for the differential responses to specific treatments. Increased proliferation and angiogenesis transforms the synovium into an aggressive, tumour-like ‘pannus’ which contributes to disease pathogenesis. Hypoxia, resulting from dysregulated angiogenesis, can cause cells to switch from mitochondrial respiration to anaerobic glycolysis in order to meet the cellular energy demand. The RA synovium is more hyperplastic and invasive than that of PsA, while a more abnormal vasculature is observed in the PsA synovium and correlates with a reduction in tissue pO2 levels.ObjectivesThe aim of this study was to compare the metabolic profiles of RA and PsA synovial fibroblast cells (SFC) and to determine whether there is a correlation between dysregulated metabolism, cell function and disease pathogenesis.MethodsThe metabolic profiles of RA and PsA SFC were analysed using the XF96 Extracellular Flux Analyzer. Gene expression was determined by quantitative-PCR. SFC migration and invasion were observed by microscopy following wound-scratch and transwell invasion assays.ResultsRA SFC displayed increased migratory capacity and invasiveness compared to PsA SFC. Expression of IL-6, IL-8 and the glycolytic markers, GLUT1/3, HK2, PKM1/2, PDK2 and LDHA is higher in RA SFC compared to PsA SFC and is upregulated following TNF-α treatment. PsA SFC displayed higher baseline oxygen consumption rate (OCR), baseline extracellular acidification rate (ECAR) and ECAR:OCR ratio than RA SFC. Treatment with TNF-α increases the ECAR:OCR ratio in both RA and PsA SFC.ConclusionsConsistent with clinical observations, RA SFC have a greater migratory and invasive capacity than PsA SFC. Despite the lower expression of glycolytic markers, PsA SFC display a more glycolytic phenotype than RA SFC, as indicated by a higher ECAR:OCR ratio. Interestingly, however, RA SFC display a higher glycolytic reserve, possibly due to the higher expression of glycolytic markers, which can be called upon in response to increases in cellular ATP demand. Preliminary data suggest a positive correlation between the ECAR:OCR ratio and DAS28 in RA but a negative correlation in PsA. Further investigation is required to determine the precise role of metabolism in specific pathogenic processes.Disclosure of InterestNone declared.

Porphyromonas gingivalis -Stimulated Hyperglycemic Microenvironment Alters the Immunometabolism of Dendritic Cells

“…Besides their role in interconnecting the chronic inflammatory states in periodontitis and DM, such increase in these pro-cytokines may help in developing other autoimmunity in innate immune cells as well. Recent studies have shown that TNF-α could stimulate the synovial fibroblast cells to increase the glycolysis related-proton efflux and promote rheumatoid arthritis, which is another risk factors associated with both periodontitis and DM (59). Similarly, in autoimmune disease Sjögren syndrome as well the inflammatory response between TNF-α and DC via TLR-7 and TLR-9 has been confirmed (60).…”