engleski

The role of immune semaphorins in NAFLD-a pilot study

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is associated with chronic low-grade inflammation, impaired immune response and microvascular endothelial dysfunction. Semaphorins, a large family of biological response modifiers, were recently recog- nized as one of the key regulators of immune response, possibly also associated with chronic liver diseases. However, their role in NAFLD has not been described. The aim of this study was to identify semaphorins associated with NAFLD and to investigate relationship with steatosis and fibrosis stages. Method: This was a prospective, multicentric, case- control study. The degree of steatosis was estimated using the controlled attenuation parameter (CAP) and transient elastography (TE) was used to measure fibrosis stage. A routine clinical, demographic, anthropo- metric and laboratory data were collected and serum semaphorin concentrations (SEMA3A, −3C, −4A, −4D, −5A and −7A) were measured by ELISA. Immunohistochemical staining of liver tissue was performed. The correlation between serum semaphorin con- centrations and steatosis and fibrosis grade was analyzed. Results: Ninety-five patients with NAFLD (51.6% males ; median age of 54, IQR 44-56 years) and 35 controls (40% males, 41, IQR 31–52 years) were included. Patients with NAFLD more frequently had diabetes mellitus (30.5% vs 8.6%), arterial hypertension (49.5% vs 8.6%), dyslipidemia (28.4% vs 11.4%) and obesity (BMI 31 kg/m2 vs 24 kg/ m2). 39 patients with NAFLD had no fibrosis (F0), and in 27, 15, 6 and 8 patients F1 to F4 was detected, respectively. A significantly higher serum concentrations of SEMA3A, −3C and −4D, and lower of SEAMA5A and −7A were found in NAFLD group compared to the healthy controls. There was no difference in semaphorin concentra- tions according to steatosis grade, but there was significant difference according to fibrosis stage, SEMA3A being lower and SEAMA3C and −4D higher in advanced fibrosis. Immunohistochemistry confirmed the higher expression of SEMA3C and SEMA4D in advanced fibrosis. Conclusion: We provide the first evidence that immune semaphorins are a promising marker of liver fibrosis in patients with NAFLD. Due to their immunomodulatory role, they could be useful in predicting liver capacity to answer challenges of infection, but also potential diagnostic and therapeutic targets in NAFLD.

immune semaphorins, NAFLD, inflammation

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