Identifying the Trigger for Psoriatic Arthritis

Psoriatic arthritis (PsA) is a complex disease that involves multiple inflammatory pathways and develops in approximately one-third of patients with psoriasis. However, not only is there no cure for PsA, but it isn’t understood what triggers the onset of PsA.

New research may have identified the trigger that activates PsA in patients, according to a study published in Nature Communications. The researchers used single-cell technology to analyze thousands of immune cells obtained from patients with PsA.

“Our data suggest that psoriatic arthritis doesn’t just appear out of nowhere,” author Hussein Al-Mossawi, BMBCh, MRCP, DPhil, honorary research associate at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) at the University of Oxford, said in a statement.

Al-Mossawi and his colleagues were able to use the technology to see which genes were switched on in each cell, which showed that the T cells had an activated inflammatory profile. They found that many T cells in the joint fluid they obtained from patients shared an identical T cell receptor—they were clones of each other. The clones of the T cells also shared other markers, including a receptor called CXCR3.

“Each receptor is like a unique lock that recognizes a molecular key and we discovered, that across the patients, they are recognizing a common molecule,” Al-Mossawi said. “This gives the first evidence that the T cells are seeing and reacting to the same molecule, which acts as a trigger for the disease. We don’t know the exact culprit yet, but this a great step forward in understanding the disease.”

The study showed increased CXCR3 gene expression, and the authors suggested that CXCR3+ T cells may play “a central role in executing localised inflammation in PsA, and thus represent an attractive therapeutic target.”

“Our findings indicate that specific T cells are likely to be targeted to enter the joint, where they are triggered to expand, creating inflammation and causing psoriatic arthritis,” said Paul Bowness, BMBCh, DPhil, professor of experimental rheumatology at NDORMS at the University of Oxford. “The next stage of research will be to find the key that is unlocking the disease in patients—from the signals that direct cells to the joint, to what then triggers them to expand. If we can understand these, we could move towards creating therapies that would prevent this, potentially providing a cure.”

Reference

Penkava F, Del Castillo Velasco-Herrera M, Young MD, et al. Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis. Nat Commun. 2020;11(1). doi:10.1038/s41467-020-18513-6