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Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
Effect of IL-12B, IL-2, TGF-β1, and IL-4 polymorphism and expression on hepatitis B progression
Roli Saxena1, Yogesh Kumar Chawla, Indu Verma
11 Department of Biochemistry, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
Insights
Specific cytokine gene variations influence hepatitis B virus (HBV) disease progression and hepatocellular carcinoma (HCC) risk in India. Certain genotypes of IL-12B, TGF-β1, and IL-2 are linked to HCC development, while IL-4 may affect disease progression to cirrhosis.
Area of Science:
- Immunogenetics
- Hepatology
- Oncology
Background:
- Chronic inflammation from hepatitis B virus (HBV) infection is a primary driver of disease chronicity.
- Cytokines are crucial in orchestrating inflammatory responses during HBV pathogenesis.
Purpose of the Study:
- To investigate the association between specific genotypes and expression levels of IL-12B, IL-2, TGF-β1, and IL-4 with HBV-related hepatocellular carcinoma (HCC) risk in an Indian population.
- To explore the role of these cytokines in the chronicity and progression of HBV infection.
Main Methods:
- Genotyping of IL-12B(+1188), IL-2(-330), TGF-β1(-509), and IL-4(-590) using PCR-based methods (PCR-RFLP, AS-PCR).
- Quantification of cytokine mRNA and protein levels via RT-PCR and ELISA, respectively.
- Analysis of 403 subjects, including controls, HBV carriers, chronic hepatitis patients, cirrhotics, and HCC patients.
Main Results:
- The IL-12B(+1188) CC genotype showed a positive association with hepatitis in controls.
- TGF-β1(-509) TT genotype was a potential protective factor against cirrhosis and HCC risk in carriers.
- IL-4(-590) CT genotype demonstrated a protective role against hepatitis development in carriers.
- IL-12B, TGF-β1, and IL-2 appear involved in HCC development, while IL-4 may influence progression to cirrhosis.
Conclusions:
- Genetic variations and expression levels of IL-12B, IL-2, IL-4, and TGF-β1 play a significant role in HBV disease chronicity and HCC development in the Indian population.
- These findings highlight potential genetic markers for predicting HBV disease outcomes and HCC risk.
Abstract:
The hepatitis B virus (HBV) infection-induced chronic inflammation is considered to be the major etiological factor for HBV-related disease chronicity. Cytokines act as the key coordinators of the inflammatory responses involved in HBV disease pathogenesis. The present study assessed association among IL-12B(+1188), IL-2(-330), TGF-β1(-509), and IL-4(-590) genotypes; mRNA; and protein levels with HBV-hepatocellular carcinoma (HCC) risk in India. For this, 403 subjects (153 controls, 67 inactive HBV-carriers, 62 chronic-active HBV patients, 62 HBV-cirrhotics, and 59 HBV-HCC ssubjects) were enrolled in the study. The genotyping was carried by polymerase chain reaction (PCR)-restriction fragment length polymorphism (IL-12+1188A/C, IL-2-330T/G, and TGF-β1-509C/T), and allele specific (AS)-polymerase chain reaction (IL-4-590C/T). Enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction methods were used for assessing protein and the mRNA expression, respectively, of the mentioned cytokines. The study revealed that the IL-12B(+1188) CC genotype shared a significant positive association with hepatitis, among controls. While, in the case of IL-2(-330), both the TG and GG genotypes were not significantly associated with HCC risk. The TGF-β1(-509) TT genotype acted as a potential protective factor for cirrhosis and the HCC risk, among carriers. On the contrary, the IL-4(-590) CT genotype was found to be a vital protective factor for the development of hepatitis, among carriers. Besides, IL-12B, TGF-β1, and IL-2 seem to be majorly involved in the development of HCC, while, IL-4 might be responsible for the progression of the HBV disease till cirrhosis development. These initial findings are indicative of the vital role of genotypes and/or levels of IL-12B, IL-2, IL-4, and TGF-β1 in HBV disease chronicity in Indian population.
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