New Tech Provides Insights Into the Pathogenesis of Psoriatic Arthritis

These results indicate that modulation of molecules orchestrating monocyte/macrophage migration or functions are also critical therapeutic targets in PsA.

Examining Psoriatic Tissue

The studies outlined above focused on cells in the synovial fluid but we do not know how well these findings reflect ongoing events in psoriatic synovial tissue. Ultrasound-guided needle biopsies permit the retrieval of high-quality synovial tissue that can be dissociated and analyzed by CyTOF and scRNAseq to provide information about the molecular profiles and subsets of resident and tissue infiltrating cells.

Newer technologies, however, provide much needed information on cell-cell interactions in target tissues. The application of novel high-throughput imaging technologies, such as spatial transcriptomics, CyTOF imaging, co-detection by indexing (CODEX) and multiplexed error-robust fluorescence in situ hybridization (MerFISH), generates data visualizing the strategic positioning, distribution and interactions of cells in target tissues.

These novel imaging technologies will provide vital insights into the diverse cell subsets along with their distribution and cellular interactions that, if adequately targeted, have strong potential to disrupt both skin and synovial disease pathways in PsA.

The efforts to apply the above technologies to the study of psoriatic skin, synovium and blood will soon be set into motion with establishment of the Accelerating Medicine Partnerships Autoimmune and Immune-Mediated Diseases (AMP AIM) in the U.S. and Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES) in Europe and the United Kingdom.

These consortia, composed of partnerships between pharmaceutical companies, academic sites and, in the U.S., the National Institutes of Health, will assemble large well-phenotyped patient cohorts to collect skin and synovial biopsies coupled with blood samples.

These tissues will be analyzed with the technologies outlined above to better understand the function and cell-cell interactions of critical effector cell subsets and molecular pathways. It is anticipated that these studies will provide a highly detailed and integrative picture of the cellular and molecular landscape in PsA target tissues.

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Maria de la Luz Garcia-Hernandez, PhD, is a research assistant professor in the Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University of Rochester, N.Y. She investigates the mechanisms of altered bone remodeling in PsA and the phenotype and contribution of synovial CD8 T cells during the transition of psoriasis to PsA using a humanized mouse model.

Christopher Ritchlin, MD, MPH, is a professor of medicine in the Allergy, Immunology and Rheumatology Division and the Center for Musculoskeletal Research at the University of Rochester Medical Center. His research team is focused on understanding psoriatic arthritis pathogenesis and the mechanisms that underlie the transition from psoriasis to psoriatic arthritis.