Researchers Analyze Skin and Joints to Unlock the Psoriatic Arthritis Microenvironment

The pathophysiology driving psoriatic arthritis (PsA) is unique compared to other forms of inflammatory arthritis. Identification of individual mechanisms that play a clear role in driving joint disease has proven challenging for researchers.

During Getting Skin and Joint in the Game: Key Players in the Psoriatic Arthritis Microenvironment, three specialists will explore recent work that describes key biologic processes, including perturbations in immune and stromal cells and the microbiome. The Wednesday, Nov. 15, session will begin at 9:15 a.m. PT in Room 25 A-B of the San Diego Convention Center. It will be available on demand within 24 hours for registered ACR Convergence 2023 participants.

“We have many therapies for PsA. Over 18 have been approved by the Food and Drug Administration in the United States,” explained Christopher Ritchlin, MD, MPH, University of Rochester. “Yet, patients who achieve full remission are still quite rare. So, we are trying to identify new inflammation pathways that we may not understand yet to improve therapeutic outcomes for our patients.”

He will highlight how humanized mouse models can help researchers better understand PsA. Mice lack T cells and B cells, which means they don’t have an immune system like humans. Dr. Ritchlin shared an abstract at ACR Convergence 2022 that showed when mice were injected with peripheral blood cells from patients with psoriasis or PsA, along with the patient’s serum, the mice also developed psoriasis and arthritis, which recapitulated the disease in the patient.

“We can go into these tissues, pull out the cells, and study them to try and understand the pathways being triggered in those cells traveling to the joint and those traveling to the skin versus what we find in the blood,” Dr. Ritchlin said. “These models may more appropriately phenocopy what’s happening in patients than the current genetic and cytokine models currently in use.”

Jose U. Scher, MD, New York University School of Medicine, will focus on how microbiome changes in the skin and the gut might drive or perpetuate PsA.

“We are working to understand whether the microbes that live within or on our body cavities, particularly the skin, and intestine, can now be correlated with not only disease states but also whether they can modulate initiation and perpetuation of skin and joint inflammation,” explained Dr. Scher, the Steere Abramson Associate Professor of Medicine, Director of the NYU Center for Autoimmunity, and Associate Director for Research and Translational Medicine in the Division of Rheumatology at the NYU Grossman School of Medicine, Director of the NYT Health Psoriatic Arthritis Center, and Director of the Microbiome Center for Rheumatology and Autoimmunity, NYU-Langone Orthopedic Hospital.

The microbiome may play a key role in understanding disease beyond the development of therapeutics.

“The microbiome may also be helpful in terms of biomarker discovery,” he said. “Many in the field are now focused on understanding whether gut microbiomes can metabolize drugs we prescribe in the clinic and if they can potentially serve as predictors of treatment response, which isn’t a minor revelation.”

Ursula Fearon, PhD, Professor of Molecular Rheumatology, Clinical Medicine, at Trinity College Dublin, Ireland, will analyze the use of synovial tissue to understand the cellular pathways and messengers released in the joint. Traditionally, researchers have searched for insights in this area by studying subjects’ blood. However, sampling skin and synovial tissue in the blood could provide insights into the underlying mechanisms in the joint that are driving PsA.