Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

Abstract

Objective: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

Approach: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

Results: Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8-8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (β=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (β=0.53; P=0.02) and vascular inflammation (β=0.48; P=0.02).

Conclusions: Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.

Keywords: CT; PET; inflammation; neutrophils; psoriasis; vascular inflammation.

Figure 1

Flow diagram depicting recruitment scheme for the study.

Figure 2. Regression plots for multivariable adjusted linear regression of psoriasis severity with aortic vascular inflammation

(A) Tomographic fused PET image of the aortic arch from a patient with severe skin disease and a control patient. (B) Regression plots for multivariable regression analysis of vascular inflammation as measured by TBR with psoriasis area and severity index (PASI) score.

Figure 3

Proteins involved in innate immunity and neutrophil modulation are higher in plasma from patients with psoriasis versus controls.

Figure 4. Neutrophil frequencies and mean fluorescence intensities in psoriasis versus control patients

(A) Representative flow cytometry plots and (B) corresponding frequencies of total neutrophils in whole blood. Neutrophils were defined as CD3^-CD19^-CD15⁺SSC^Hi and are presented as percentage of viable cells. (C) Mean fluorescence intensity (MFI) of CD62L and CD16 were obtained from the total neutrophil gate.

Figure 5. Proteins associated with neutrophils are increased in psoriasis

Neutrophil biomarkers myeloperoxidase (MPO), S100A8/A9, and neutrophil elastase (NE1), respectively, from psoriasis and control patient serum.

Figure 6. Circulating S100A8/A9 levels are associated with psoriasis severity as well as vascular inflammation by FDG PET/CT

(A) Regression plots for multivariable regression analysis of S100A8/A9 with psoriasis area and severity index (PASI) score for untreated psoriasis patients. (B) Regression plots for multivariable regression analysis of S100A8/A9 with vascular inflammation as measured by TBR.