Psoriatic disease is associated with systemic inflammation, endothelial activation, and altered haemostatic function

Abstract

Psoriasis is a chronic, immune-mediated inflammatory skin disease, affecting approximately 2% of the general population, which can be accompanied by psoriatic arthritis (PsA). The condition has been associated with an increased cardiovascular burden. Hypercoagulability is a potential underlying mechanism that may contribute to the increased risk of major cardiovascular events in psoriatic individuals. Whole blood samples were collected from 20 PsA patients and 20 healthy individuals. The concentrations of inflammatory molecules (C-reactive protein, serum amyloid A, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble P-selectin) were determined by enzyme-linked immunosorbent assays. In addition, clotting efficiency was evaluated by thromboelastography. The fibrin network architecture was also assessed by scanning electron microscopy. Elevated levels of circulating inflammatory molecules were significantly associated with the presence of psoriatic disease. Furthermore, an increased tendency towards thrombus formation was significantly predictive of disease presence. Scanning electron microscopy revealed that fibrin clots were denser in psoriatic individuals, compared to healthy controls, with an increased fibrin fibre diameter associated with psoriatic disease. Our results add to the accumulating evidence of the systemic nature of psoriasis and the subsequent risk of cardiovascular comorbidities, potentially due to an acquired hypercoagulability. We suggest that haemostatic function should be monitored carefully in psoriatic patients that present with severe disease, due to the pre-eminent risk of developing thrombotic complications.

Figure 1

Representative scanning electron micrograph with grid overlay. Numbered fibres indicate fibres that were measured. Individual grid blocks represent an area of 2 μm². Total grid area is 97 μm² (scale bar = 1 μm).

Figure 2

Box-and-whisker plots illustrating the distribution of parameters assessed in this study in healthy individuals and psoriatic patients. (A–D) indicates V-PLEX panel results, (E) indicates sSELP ELISA results, (F–L) indicates TEG results, and (M–O) indicates fibrin fibre diameter results. Asterisks indicate statistically significant differences between the groups, as determined by either an unpaired t-test or Mann–Whitney test, where ****p < 0.0001, ***p < 0.001, **p < 0.01, and *p < 0.05. Box-and-whisker plots were produced using GraphPad Prism version 8.4.3.

Figure 3

(A–D) Representative scanning electron micrographs of fibrin networks (prepared form PPP) from a healthy individual and psoriatic patients. (A) A typical fibrin network of a healthy 47-year-old female individual. (B–D) Fibrin networks of psoriatic individuals. (B) A fibrin network of a 45-year-old female individual with low PsA activity and mild skin involvement. (C) A fibrin network of a 40-year-old male individual with moderate PsA activity and mild skin involvement. (D) A fibrin network of a 49-year-old male individual with high PsA activity and moderate skin involvement.

Figure 4

Frequency bar graphs of fibrin fibre diameter distribution. (A) indicates healthy individuals and (B) indicates psoriatic patients. Bar graphs were produced using GraphPad Prism version 8.4.3.

Figure 5

A summary of the key findings of this study. Various pro-inflammatory molecules are implicated in the onset and maintenance of psoriatic disease. These inflammatory mediators may spill over into circulation, resulting in systemic inflammation. Accordingly, psoriatic patients presented with elevated levels of acute-phase reactants (CRP and SAA). As the processes of inflammation and coagulation are interconnected, persistent systemic inflammation may promote the development of a prothrombotic state in psoriatic individuals. In this study, the prothrombotic state in psoriatic patients were characterised by endothelial (elevated sICAM-1 levels) and platelet activation (elevated sP-selectin levels), hypercoagulability (TEG results), and abnormal fibrin deposition (SEM analysis). Diagram created with BioRender.com.