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Researchers identify two inflammatory-driving proteins, osteopontin and CCL2, highly expressed in psoriatic arthritis joints.

Hands of a person with psoriatic arthritis © Shutterstock

Little is known yet about the cause of psoriatic arthritis (PsA), a condition that can lead to swelling and pain in the joints of patients with skin psoriasis, but research has moved a step forward with the publication of a new paper in the Annals of the Rheumatic Diseases

The purpose of the research was to gain a deeper understanding of the inflammatory processes in PsA by studying the synovial fluid from patients.

Led by Dr Hussein Al-Mossawi, Honorary Research Associate, and Professor Paul Bowness at the Botnar Research Centre, NDORMS, the study found that a subset of immune cells, called myeloid cells, are highly activated in the joint compared to blood. These cells spontaneously produce significant amounts of proinflammatory factors, specifically the proteins osteopontin and CCL2.

The study used two main methodologies to generate a high-dimensional dataset. The first was mass cytometry, which enables simultaneous measurement of over 30 protein parameters for each cell followed by an unsupervised clustering analysis. The second method, transcriptomic analysis, both gene array and single-cell RNA sequencing, was used to confirm both the specific genes that are dysregulated and the cell types involved. For the mass cytometry assay, fresh synovial fluid and matched blood were taken and analysed immediately to capture the profile in the joint as accurately as possible.

Dr Nicole Yager, Postdoctoral Research Assistant in Immunology at the Botnar Research Centre and the lead author of the paper explained: "While the majority of studies of the inflammatory environment in PsA use in vitro stimulation to amplify the response, it can be difficult to relate these findings back to the cells in the disease state. Our approach of using mass cytometry, which itself has revolutionised the way samples can be immunophenotyped, without external stimulation, resulted in the identification of two highly interesting proinflammatory proteins in the synovial fluid myeloid compartment. It is exciting to consider the potential of either of these proteins on a diagnostic basis or as novel therapeutic benefit for PsA."

Dr Hussein Al-Mossawi said: "The approach we have taken here has allowed us to identify potentially important and under-appreciated molecules such as osteopontin and CCL2 which can be targets for new treatments in psoriatic arthritis."

The research was funded by UCB.

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