Serum Semaphorin Alterations in Psoriasis: Links to Metabolic Status Rather than Disease Severity

Psoriasis is an autoimmune systemic disease of not entirely understood pathogenesis. It remains a significant therapeutic challenge and, due to its various comorbidities, has a remarkable detrimental effect on patients' wellbeing. Semaphorins (Sema) are a group of transmembrane, cell surface-attached and secretory proteins that might play an important role in psoriasis due to their presence on keratinocytes and the ability to stimulate the proinflammatory cytokine production.

The study aimed to assess the concentration of Sema3A, Sema3E, Sema4A, Sema4D and Sema7A in serum samples of psoriatic patients and explore the correlation with disease activity and clinical and metabolic status.

The study involved 60 patients with plaque psoriasis and 30 healthy volunteers matched for gender, age, and BMI.

The mean serum Sema3A, Sema3E and Sema4D levels were significantly higher in patients with psoriasis than controls (p < 0.01, p < 0.05 and p < 0.05, respectively). Contrarily, Sema4A and Sema7A were significantly lower (p < 0.001 and p < 0.05 respectively). Significant positive correlation between Sema3A and UREA was noted. Sema3A levels were significantly higher in moderately ill and overweight patients (p < 0.05, p < 0.01, respectively) and in patients with longer-lasting psoriasis and male patients compared to controls (both p < 0.05). Sema3E significantly negatively correlated with HDL and glucose levels. Sema4A was significantly lower in moderately and severe psoriatic patients (p < 0.0001, p < 0.01, respectively). Sema7A was significantly higher in moderately ill and overweight patients (p < 0.05, p < 0.01, respectively) and significantly lower in male patients and in those with longer lasting disease than in controls. None of the semaphorins correlated with psoriasis severity, total BMI, psoriasis duration and age.

Psoriatic patients exhibited distinct alterations in circulating semaphorins, with significantly increased serum Sema3A, Sema3E and Sema4D, and reduced Sema4A and Sema7A compared with healthy subjects. Selected semaphorins demonstrated associations with metabolic parameters and patient characteristics, although none can serve as marker of disease severity. The findings indicate that semaphorins may reflect psoriasis-related systemic disturbances, but further studies are required to explore their potential with disease-associated metabolic or clinical profiles.