Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection

Hegazy, Doha; Thurairajah, Prem Harichander; Metzner, Magdalena; Houldsworth, Annwyne; Shaw, Steve; Kaminski, É.; Demaine, A. G.; Cramp, Matthew

doi:10.1111/j.1365-2249.2008.03655.x

Cited by 27 publications

(25 citation statements)

References 25 publications

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“…Th1 cellular immune responses are important for effective clearance of HCV viraemia [18–21] and IL‐12 is considered a key cytokine in promoting a Th1 response. A functional single nucleotide polymorphism in IL12B gene has previously been found to be associated with this EU cohort [22]. However in this study IL‐12 levels were low in EU, which demonstrates the challenges with extrapolation of functional correlates from single nucleotide genetic associations.…”

Section: Discussionmentioning

confidence: 67%

Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection

Warshow

Riva

Hegazy

et al. 2012

Journal of Viral Hepatitis

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A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment-naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV-Ab+ and HCV-RNA-) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL-6 (on average more than 100-fold, P = 0.001) and IL-8 (on average more than 10-fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor-alpha (TNF-α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon-alpha (IFN-α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro-inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin-6 and interleukin-8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort.

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Section: Discussionmentioning

confidence: 67%

Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection

Warshow

Riva

Hegazy

et al. 2012

Journal of Viral Hepatitis

View full text Add to dashboard Cite

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“…A cohort of current IDU not known to have HCV infection or other blood borne viruses was recruited between 2003 and 2014 from a variety of locations in Plymouth, UK, as previously described . All individuals completed a confidential structured questionnaire to collect demographic data and a detailed injecting history.…”

Section: Methodsmentioning

confidence: 99%

“…EU cohorts are immunologically distinct from both healthy controls and those who spontaneously clear HCV infection (see Table ) . Up to 60% of EU individuals display HCV‐specific adaptive T‐cell responses.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, they display enhanced NK cell, IL6/IL8 and TNF‐α activity compared to HCV‐infected IDUs . They are also genetically distinct from spontaneous resolvers and those with chronic HCV with the combination of KIR2DL3, HLA‐C1 over represented in both the EU and spontaneous resolver groups while the prevalence of the IL28B polymorphism is similar in EU to chronically infected cohorts …”

Section: Introductionmentioning

confidence: 99%

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Anti‐envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection

Swann

Mandalou

Robinson

et al. 2016

Journal of Viral Hepatitis

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SummaryInjection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high‐risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti‐HCV‐envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty‐two hepatitis C diagnostic antibody‐ and RNA‐negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus‐neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti‐envelope antibodies. In addition to confirming viral exposure, the presence of specific anti‐envelope antibodies may be a factor that helps these individuals resist HCV infection.

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“…Inheritance of specific gene variants may alter the direction of immune responses and affect the pathogenesis of immune-mediated diseases. The associations between IL-12B gene variants and diseases such as type 1 diabetes (Morahan et al, 2001), asthma (Morahan et al, 2002), malaria (Marquet et al, 2008;Naka et al, 2009), and hepatitis C (Mueller et al, 2004;Hegazy et al, 2008) are well documented. Most gene association studies, however, were reported for Caucasian populations.…”

Section: Discussionmentioning

confidence: 99%

IL-10 and IL-12B gene polymorphisms in a multiethnic Malaysian population

Sam¹,

Teoh²,

AbuBakar³

2015

Genet. Mol. Res.

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ABSTRACT. Inheritance of polymorphisms in the interleukin (IL)-10 promoter and IL-12B genes, which influence cytokine production and activities, may define the balance in T helper response in infection and autoimmune diseases. In the present study, we investigated the distribution of the IL-10 promoter and IL-12B gene polymorphisms in a multiethnic Malaysian population. Overall, our findings suggest that the IL-12B and IL-10 -592 genotypes were distributed homogenously across all major ethnic groups, including Malays, Chinese, and Indians, except for polymorphisms at IL-10 -1082. At this gene locus, the ethnic Chinese showed a significantly lower allele frequency of -1082G (2.1%) compared to the Malay (12.2%) and Indian (15.3%) populations. Results for the IL-12B and IL-10 gene polymorphisms were consistent with those reported for the Asian population, but markedly different from those of the African and Caucasian populations. Our findings suggest that there are specific genetic variations between different ethnic groups, which should be examined in all gene population-based association studies.

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Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection

Cited by 27 publications

References 25 publications

Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection

Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection

Anti‐envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection

IL-10 and IL-12B gene polymorphisms in a multiethnic Malaysian population

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