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Archives of Virology

, Volume 161, Issue 11, pp 3161–3169 | Cite as

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients

  • Minesh Mehta
  • Helal F. Hetta
  • Enass A. Abdel-hameed
  • Susan D. Rouster
  • MdMonir Hossain
  • Mohamed A. Mekky
  • Nasr K. Khalil
  • Wegdan A. Mohamed
  • Mohamed A. El-Feky
  • Shabaan H. Ahmed
  • Enas A. Daef
  • Mohamed A. El-Mokhtar
  • Sayed F. Abdelwahab
  • Ahmed Medhat
  • Kenneth E. Sherman
  • Mohamed Tarek M. Shata
Original Article

Abstract

The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3-35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

Keywords

Treg Cell Rs12979860 Single Nucleotide Polymorphism Liver Inflammation IL28B Genotype Treg Frequency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

GWAS

Genome-wide association studies

SNP

Single-nucleotide polymorphism

PBMCs

perIpheral blood mononuclear cells

Treg

Regulatory T cells

CHC

Chronic hepatitis C

HCV

Hepatitis C virus

HCV-4

Hepatitis C virus genotype 4

SVR

Sustained virologic response

DCs

Dendritic cells

Treg

T regulatory

FoxP3

Forkhead box protein P3

IBD

Inflammatory bowel diseases

NR

Non-responder

Peg-IFN + Rib

Pegylated interferon-α and ribavirin

HPF

High-power field, 1 HPF=0.4 mm2

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

IF

Immunofluorescence

Notes

Acknowledgments

We would like to thank all of the participants in this study, particularly the patients.

Compliance with ethical standards

Conflict of interest

All authors declare that no conflict of interest exists regarding the work reported in this manuscript.

Ethical approval

Verbal and written consent was obtained from all participants according to an IRB protocol approved by the Assiut University College of Medicine Institutional Review Board.

Funding and financial support

This investigation was supported by an Egyptian Government scholarship for Helal Hetta, the Grant office, Faculty of Medicine, Assiut University, Egypt., Merck Investigator Initiated Studies (IISP #: 40458 [Shata]); National Institute of Health Grant (K24DK070528 [Sherman]); and was partially supported by Public Health Service Grant (P30 DK078392 [The Gene Expression Microarray Core Cincinnati Children’s Hospital Medical Center]); National Institute of Health Grant (NIH P30 DK078392 [Core of the Digestive Disease Research Core Center in Cincinnati]).

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Minesh Mehta
    • 1
  • Helal F. Hetta
    • 1
    • 2
  • Enass A. Abdel-hameed
    • 1
  • Susan D. Rouster
    • 1
  • MdMonir Hossain
    • 3
  • Mohamed A. Mekky
    • 4
  • Nasr K. Khalil
    • 5
  • Wegdan A. Mohamed
    • 2
  • Mohamed A. El-Feky
    • 2
  • Shabaan H. Ahmed
    • 2
  • Enas A. Daef
    • 2
  • Mohamed A. El-Mokhtar
    • 2
  • Sayed F. Abdelwahab
    • 6
  • Ahmed Medhat
    • 4
  • Kenneth E. Sherman
    • 1
  • Mohamed Tarek M. Shata
    • 1
    • 7
  1. 1.Division of Digestive Diseases, Department of Internal MedicineUniversity of Cincinnati Medical CenterCincinnatiUSA
  2. 2.Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
  3. 3.Division of Biostatistics and EpidemiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  4. 4.Department of Gastroenterology and Tropical Medicine, Faculty of MedicineAssiut UniversityAssiutEgypt
  5. 5.Assiut Liver Institute for Treatment of Hepatitis CAssiutEgypt
  6. 6.Department of Microbiology and Immunology, Faculty of MedicineMinia UniversityMinyaEgypt
  7. 7.Department of MicrobiologySaint James School of Medicine, Saint VincentArnos ValeSaint Vincent and the Grenadines

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