A pilot study on some critical immune elements in HBV infection: evidence of Alpha-1 Antitrypsin as an immunological biomarker

AIM: This study is an attempt to screen the key immune elements that participate during HBV infection and the related pathways that are modulated. BACKGROUND: The pathogenesis of Hepatitis B virus and the corresponding clinical manifestations in the host are primarily immune-mediated. METHODS: This study utilizes a PCR array to screen immune-related genes that are differentially expressed in the presence of the virus in HBV replicating HepG2.2.15 cells as compared to control HepG2 cells. The significantly up-regulated genes were subjected to bioinformatic analysis utilizing GSEA and STRING. Additionally, ELISA was used to corroborate the levels of Alpha 1 antitrypsin (AAT) from patients’ sera. RESULTS: The expressions of 31% of the studied genes were significantly up-regulated (> 2-fold, p<0.05) in HepG2.2.15 cells compared to controls, and this included the SERPINA1, FN1, IL1R2, LBP, LY96, LYZ and PROC genes. When they were clustered based on biological processes, signaling pathways, and disease progression, the genes related to biotic stimulus, complement-coagulation cascades, and fibrosis, respectively, showed the highest (p<0.05) enrichment. Analysis of patients’ sera by ELISA revealed that the serum AAT (SERPINA1) levels were significantly higher in asymptomatic carriers and in patients with chronic liver disease than in controls (p<0.05). Moreover, SERPINA1 levels were also positively correlated with the levels of serum ALT (r=0.4495, p<0.05) among HBV infected patients. CONCLUSION: The current study highlights the key immune elements and pathways that are modulated during HBV infection and proposes the possible use of AAT as a non-invasive immunological biomarker to follow the progression of liver disease.