Deep cellular immune profiling of psoriatic arthritis linked to imaging phenotypes and targeted therapy response
Presenter: Lihi Eder, MD, PhD, Associate Professor of Medicine, Canada Research Chair in Inflammatory Rheumatic Diseases, University of Toronto, Toronto, ON, Canada
Deep Cellular Immune Profiling in Psoriatic Arthritis Correlates with Imaging Phenotypes and Response to Targeted Advanced Therapy. Abstract 1689. Presented Nov 13, 2023.
Immune cell phenotypes are associated with some sonographic features of psoriatic arthritis (PsA) and response to therapy, researcher Lihi Eder, MD, PhD, reported at the ACR Convergence 2023. The findings suggest that immune cell profiling can help risk stratify patients and identify those who are more difficult to treat.
“Such patients may benefit from earlier and more intense regimens, and possibly from combination therapy,” said Dr Eder, Associate Professor of Medicine and Canada Research Chair in Inflammatory Rheumatic Diseases at the University of Toronto, Toronto, ON, Canada.
In their study, Dr Eder and co-investigators recruited patients with PsA who were starting treatment for active peripheral musculoskeletal disease with therapies that went beyond conventional treatment. Investigators used mass cytometry on whole blood to characterize immune cell populations and how it aligns with disease features and response to therapy.
Results showed that CD4+ memory and Th1 cells were associated with more severe synovitis and enthesitis as well as poor response to advanced therapies. By contrast, γδT cells and CD8+ naive cells were correlated with milder disease phenotype and improved response to treatment.
The study encompassed 40 treatment periods involving 34 unique patients, including 21 treated with an interleukin-17 inhibitor, 16 treated with a tumor necrosis alpha inhibitor, and 3 treated with a Janus kinase inhibitor. Overall, 60% of patients achieved an ACR20 response.
In cluster analyses, researchers identified three distinct immune cell profiles:
- In Cluster 1, γδT cells and CD8+ naive cells were predominant. This cluster was associated with lower inflammation, lower Physician Global Assessment, and younger patient age.
- In Cluster 2, central memory and effector memory CD4+ T cells were predominant. This cluster was associated with the highest levels of sonographic inflammation, especially regarding joints and entheses and older age.
- In Cluster 3, CD4+ and CD8+ terminal effector T cells and Th1 cells were predominant. The cluster was associated with high levels of peritenon inflammation as compared to the other two clusters.
These immune cell profiles were also associated with responses to treatment, Dr Eder said. Of note, Cluster 2 was linked to a lower probability of achieving an ACR20 response or an increase in Disease Activity index for PsA (DAPSA) score as compared to the other clusters.
Looking at specific cell populations, higher levels of CD8+ cells were associated with reduction in DAPSA, while higher levels of γδT cells correlated with higher likelihood of ACR20 response, and higher levels of naive effector memory and central memory CD4+ and Th1 cells were linked to lower treatment response.
Th1 and γδT cell levels also predicted change in sonographic inflammatory score, according to the report.
In the interview, Dr Eder said that she and her colleagues continue to study immune cell profiling with more patients, with the aim of assessing whether this practice can inform the selection of treatment strategies with specific modes of action.
“The results of immune cell profiling using mass cytometry seems promising in identifying patients that are difficult to treat,” Dr Eder said.
However, more research is needed to assess if this method could be used to inform selection of targeted disease-modifying anti-rheumatic drugs, she added.
Disclosures
Lihi Eder, MD, PhD, reported disclosures related to AbbVie, Eli Lilly, Fresenius Kabi, Janssen Pharmaceuticals, Novartis, Pfizer, Sandoz, and UCB.