Skin & Joints: Experts Discuss Advances in PsA

They also found that CX3CR1 macrophages, which interact with fibroblasts in healthy joints to form a protective barrier, break down in RA and PsA.

“In RA, the protective macrophage barrier is completely depleted,” Dr. Fearon said.

She said further work should be done to understand the interactions between immune and stromal cells, to help distinguish between the pathotypes of RA and PsA and pathotypes within each disease.

“We know within RA and PsA there are different pathotypes of these diseases,” she said, “and this could have implications for their therapeutic response.”

The Microbiome

Jose Scher, MD

Jose Scher, MD, director of the New York University Psoriatic Arthritis Center, said his lab’s work on the microbiome and rheumatic disease has turned to the role of short-chain fatty acids.

Although a significant reduction in the intestinal diversity has been seen across autoimmune diseases, he said, “it might have nothing to do with the antigenic properties of microbes.”

Gut dysbiosis in PsA correlates with decreased levels of protective fatty acids, including short-chain fatty acids, and short-chain fatty acids expand regulatory T cells in the gut and have been found to prevent inflammatory bowel disease, he said.

Levels of butyrate, a short chain fatty acid, are reduced in patients with RA, and a deficiency of butyrate-producing microbes in the gut has been seen in ACPA+, erosive RA patients, researchers have also found.

A stark reduction in butyrate levels has been seen in patients with psoriasis, right as they progress to psoriatic arthritis, more recent work has found.²

“Maybe you don’t need microbes after all,” Dr. Scher said. “Maybe all you need is short chain fatty acids to modulate systemic disease.”

Short-chain fatty acids mitigate osteoclast-mediated arthritic bone remodeling in a PsA mouse model, according to recently published work.

Early results out of his lab suggest that butyrate in the gut is decreased among those with new-onset RA who do not respond to methotrexate and that butyrate might help improve the methotrexate response, but work on this is continuing, Dr. Scher said.

“Exploiting the microbiome may be considered to enhance the effective initiation of anti-rheumatic drugs and as a potential precision medicine strategy,” he said.

A More Complex Mouse Model

Christopher Ritchlin, MD, MPH

Christopher Ritchlin, MD, MPH, professor of medicine at the University of Rochester, discussed a new mouse model developed in his lab that is able to recapitulate the characteristics of psoriatic arthritis of individual patients. Such an approach, he said, could overcome limitations of existing PsA mouse models, in which the wide-ranging disease characteristics can’t be represented.