Activation of inflammation in our cells is a key mechanism by which our body fights infection. However, if uncontrolled, the inflammatory cells don’t switch off and this can contribute to development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

In the joints of inflammatory arthritis patients many new blood vessels grow, allowing immune cells from the blood to invade into the joint. Synovial cells adapt by changing their metabolic profile to one that can more rapidly produce energy, which allows them to maintain cell activation and function.  

Therefore, if we can develop therapies that can switch synovial cells to a normal metabolic profile, we may be able to suppress inflammation. In this study we aim to examine how these pathways differ between RA and PsA, and identify if we can therapeutically block them.

To date in this project, we have obtained synovial tissue from patients and we have demonstrated there are a lot more blood vessels in PsA vs RA, with an increased invasiveness phenotype in RA.

We show this is associated with increased metabolic activity with blood vessels in PsA and with the invasive layer in RA. We then isolated the cells that reside in this invasive layer which are called ‘synovial fibroblasts’. These are the cells that invade the cartilage and bone.

We have demonstrated differential expression of metabolic and inflammatory markers in RA and PsA synovial fibroblasts, which suggests that these two diseases have different underlying mechanisms that drive disease pathogenesis. 

Interestingly while RA synovial fibroblasts migrate and invade to a greater extend to that of PsA, the PsA synovial fibroblasts have higher metabolic activity.

The invasive and metabolic profile of RA synovial fibroblasts correlates positively with disease activity, however for PsA we observed a negative correlation. We are now examining if synovial fibroblasts differ in their effects on a process called "osteoclastogenesis" which is a way of assessing their effect on bone erosion.  In future work we aim to identify if blockade of common pathways work in both RA and PsA, or if we need to target different pathways.

Funding

This research is funded under the Health Research Charities Ireland/Health Research Board Joint Funding Scheme 2016.