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Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response

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Abstract

The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous hepatitis C virus (HCV) clearance and treatment response. The distribution and correlation of an IL28B.rs12979860 single-nucleotide polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among Egyptian healthcare workers (HCWs) is not known. We determined this relationship in 402 HCWs who serve a patient cohort with ~85 % HCV prevalence. We enrolled 402 HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2 (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients. All subjects were tested for an HCV-specific CMI response using an ex-vivo interferon-gamma (IFNγ) ELISpot assay with nine HCV genotype-4a overlapping 15-mer peptide pools corresponding to all of the HCV proteins. All subjects were tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was demonstrated in ~27 % of the seronegative aviremic HCWs (group 1), suggesting clearance of infection after low-level exposure to HCV. The frequency of IL28B.rs12979860 C allele homozygosity in the four groups was 49 %, 48 %, 49 %, and 23 %, while that of the T allele was 14 %, 16 %, 12 and 19 %, respectively, suggesting differential distributions among subjects with different HCV status. As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p < 0.05), but we did not find any relationship between the IL28B genotypes and the outcome of HCV-specific CMI responses in the four groups (p > 0.05). The data show differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with different HCV status and could not predict the outcome of HCV-specific CMI responses.

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Abbreviations

PBMC:

Peripheral blood mononuclear cells

CMI:

Cell-mediated immunity/immune response

DMSO:

Dimethyl sulfoxide

HCV:

Hepatitis C virus

IFN:

Interferon

IL:

Interleukin

PBMC:

Peripheral blood mononuclear cells

RT-PCR:

Reverse transcription polymerase chain reaction

SEB:

Staphylococcal enterotoxin B

SFC:

Spot-forming cells

SNP:

Single-nucleotide polymorphism

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Acknowledgments

We thank Mrs. Hoayda M. Ahmed (from the NLI) for her assistance with sample collection. Mrs. Enas S. Aziz (Egyblood) performed the data entry. We particularly appreciate Dr. Raied S. Ibrahim (Vacsera CEO), Dr. Gehan Galal (Director of Egyblood R&D Department), Dr. Nelly Sedky and Dr. Hala Hussein (previous and current Egyblood CEO, respectively) for their support throughout the conduct of the study.

Compliance with ethical requirements

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975. The study protocol was approved by the National Liver Institute Institutional Review Board. Informed consent was obtained from all subjects for being included in the study.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This study was supported by the Egyptian Science and Technology Development Fund (STDF) Contract no. 1664 to S.F. Abdelwahab.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Sayed F. Abdelwahab

  2. The Holding Company for Biological Products and Vaccines (VACSERA), 51 Wizaret El-Zeraa St., Agouza, Giza, 22311, Egypt

    Sayed F. Abdelwahab, Zainab Zakaria, Maha Sobhy, Shaimaa Hamdy & Walaa R. Allam

  3. Department of Microbiology, Taif Faculty of Pharmacy, Al-Haweiah, PO Box 888, Taif, 21974, Kingdom of Saudi Arabia

    Sayed F. Abdelwahab

  4. Department of Hepatology, National Liver Institute, Menoufiya University, Menoufiya, 32511, Egypt

    Mohamed A. Mahmoud, Eman Rewisha & Imam Waked

  5. South Egypt Cancer Institute, Asyut, 71526, Egypt

    Nabiel Mikhail

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  1. Sayed F. Abdelwahab
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  2. Zainab Zakaria
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Correspondence to Sayed F. Abdelwahab.

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Abdelwahab, S.F., Zakaria, Z., Sobhy, M. et al. Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response. Arch Virol 160, 1741–1750 (2015). https://doi.org/10.1007/s00705-015-2446-7

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