An analysis of microarray data demonstrated impaired apoptosis signaling pathways in CD14+ monocytes in psoriatic arthritis patients, concluding that their increased levels may play an essential role in the disease pathogenesis.
Psoriatic arthritis (PsA) is a complex chronic inflammatory condition affecting approximately 30% of patients with psoriasis, leading to functional impairments and increased mortality risk.
Osteoclast activity is a crucial aspect of the erosion of bones observed in PsA. Osteoclasts, derived from monocyte/macrophage lineage precursors, play a pivotal role in bone resorption. Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) also play essential roles in osteoclastogenesis. Furthermore, the expansion of osteoclast precursors in the bone marrow of PsA patients underscores the importance of understanding osteoclast biology in the disease.
Elevated levels of tumor necrosis factor-alpha (TNF-α) in both the skin and joints of psoriasis patients contribute to inflammation by inducing the production of monocyte chemotactic protein-1 (MCP-1) and recruiting osteoclast precursors into joint tissues. This highlights the role of TNF-α in perpetuating inflammation in PsA and underscores its significance as a therapeutic target.
Cell apoptosis in immune cells plays an important role in immune regulation and has been found to be dysregulated in some autoimmune diseases, including PsA. In particular, apoptosis plays an important role in regulating monocyte activity in PsA. Hence, this study aimed to uncover novel insights into the immunological dysregulation characteristic of PsA to determine how apoptotic death in these monocytes influences inflammation.
This study, published in the journal Biomedicines, focused on apoptosis dysregulation of monocytes, as they are the precursors to macrophages and osteoclasts. Understanding the topic will enhance understanding of the disease pathogenesis.
Reduced Apoptosis and Activity of CD14+ Monocytes Observed in Psoriatic Arthritis Patients
The study focused on various factors contributing to the development and progression of PsA, including biomechanical strain, cutaneous inflammation, and metabolic factors. These factors were implicated in recruiting abnormal immune cells, particularly to the enthesis, where high mechanical strain can cause microdamage, triggering inflammation characterized by the infiltration of macrophages, lymphocytes, and neutrophils.
The study enrolled patients diagnosed with PsA based on established criteria, and age- and sex-matched healthy controls. Peripheral CD14+ monocytes were isolated from blood samples and subjected to gene expression analysis using microarray and quantitative polymerase chain reaction (qPCR) assays. Flow cytometry was employed to assess apoptotic activity in monocytes, providing valuable insights into the functional characteristics of these cells in PsA patients.
The results of the study revealed several key findings. Firstly, patients with PsA exhibited a higher number of peripheral CD14+ monocytes compared to healthy controls, suggesting a potential role of these cells in PsA pathogenesis. Notably, this elevated monocyte count decreased following successful biologic treatment. Microarray analysis of PsA monocytes identified downregulation of apoptosis-related genes, including cathepsin L (CTSL), which was confirmed by qPCR. Flow cytometry revealed impaired apoptotic activity in PsA monocytes, highlighting a potential mechanism contributing to the persistence of inflammation in the disease.
The Bottom Line
The study provides valuable insights into the molecular mechanisms underlying PsA. It demonstrated impaired apoptosis in CD14+ monocytes in PsA patients and their increased peripheral count. It also showed that reducing monocyte count using various therapeutic approaches was beneficial. These findings may help find more effective treatment approaches targeting disease pathogenesis.
Source:
Tasende, J. a. P., Fernández-Moreno, M., Rego‐Pérez, I., Fernandez-Lopez, J., Oreiro-Villar, N., De Toro Santos, F. J., & Blanco, F. J. (2024). Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics. Biomedicines, 12(4), 815. https://doi.org/10.3390/biomedicines12040815
