Neutrophils from patients with psoriatic arthritis (PsA) exhibit impaired function and altered activity, potentially contributing to the severity and progression of the disease, according to a new study published in Frontiers in Immunology. The research, which compared neutrophil behavior in PsA patients and healthy controls, reveals a distinct neutrophil phenotype associated with the inflammatory condition.
Impaired Neutrophil Function in PsA
The study evaluated the activation status, ROS production, phagocytic activity, and release of granular enzymes and NETs from peripheral blood neutrophils of 31 PsA patients and 22 healthy controls (HCs). The researchers found that, upon stimulation with TNF, neutrophils from PsA patients displayed lower expression of activation markers (CD66b, CD11b, and CD62L), reduced ROS production, and a diminished ability to phagocytose bacterial bioparticles compared to neutrophils from HCs.
"Our data demonstrate that PMNs from PsA patients, upon TNF stimulation, exhibit diminished efficiency in several key effector functions, including activation, ROS production, phagocytosis of bacterial particles, and the release of granular enzymes and NETs," the authors stated.
Reduced Release of Granular Enzymes and NETs
Further analysis revealed that PsA neutrophils released fewer granular enzymes (MPO and MMP-9) and NET biomarkers than those from HCs, indicating impaired degranulation and NET formation. NETs, or neutrophil extracellular traps, are networks of DNA and proteins released by neutrophils to trap and kill pathogens. However, in autoimmune diseases, NETs can contribute to inflammation and tissue damage.
Elevated Serum Levels of Neutrophil Mediators
The study also found increased levels of neutrophil-related mediators MMP-9, MPO, TNF, IL-23, and IL-17, as well as elevated levels of CitH3, a specific NET biomarker, in PsA patients compared to HCs. Circulating levels of CitH3 displayed a moderate correlation with serum concentrations of MPO and TNF. ROC curve analysis demonstrated that serum levels of CitH3 could accurately distinguish PsA patients from HCs with high specificity (0.64) and sensitivity (0.90).
Clinical Implications
The findings suggest that neutrophils in PsA patients are in a state of "pre-activation," leading to reduced reactivity during subsequent in vitro stimulation. This phenomenon, known as "innate immune tolerance," may contribute to ongoing inflammatory processes and impair the role of neutrophils in host defense.
"Our findings underscore the need for a reassessment of PMNs and neutrophil-related mediators in the pathophysiology of PsA," the researchers concluded. "Further investigations involving larger cohorts of both healthy donors and patients could corroborate and better highlight the role of PMNs and neutrophil-related mediators in PsA."
