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Importance of cell-mediated immunity

A weakened immune system

The varicella zoster virus (VZV) is usually kept dormant in the dorsal root ganglia after varicella (chickenpox) by cell-mediated immunity (CMI).1-3 Subclinical reactivations throughout an individual’s lifetime are prevented by VZV-specific T-cell-mediated immunity, consisting of both CD4+ and CD8+ effector and memory T cells.1 This immunity wanes with increasing age, and immunosuppressive diseases or therapies increase the risk of VZV reactivation.3

Establishing the link between CMI and shingles

VZV-specific CMI plays a more critical role in the prevention of VZV reactivation than antibodies.4 Observations in different groups of patients support this. For example, patients with human immunodeficiency virus infection, and therefore low CD4+ and CD8+ T-cell counts, are at high risk of shingles.2,3 In patients who have received a haematopoietic stem cell transplant, CMI is depressed but antibodies against VZV are not affected; these patients are at high risk of developing shingles.2 By contrast, patients with the inherited immunity disorder X-linked agammaglobulinaemia maintain their CMI but are unable to produce antibodies. These patients are not at an increased risk of shingles.2

It is thought that antibodies play a key role in preventing primary VZV infection, while T cells are fundamental to resolving the disease, limiting severity and preventing reactivation.5

Cancer and shingles risk

It is well established that cancer increases the risk of shingles; both the type of cancer and treatment can affect the risk.6 The association between cancer and shingles risk may result from immune system dysfunction caused by certain blood cancers or the immunocompromising effects of treatment, or a combination of both.6

In an analysis of 240,000 older adults (mean age 62.0 years at recruitment) with over 8 years of follow-up, a diagnosis of any cancer was associated with a 40% higher risk of developing shingles compared with no cancer diagnosis.6 When compared with individuals without cancer, the risk of HZ in patients with blood cancers was substantially higher than in patients with solid organ cancers (adjusted hazard ratio of 3.74 [95% CI, 3.11–4.51] vs. 1.03 [95% CI, 1.21–1.40], respectively) and was also apparent in the 2 years prior to cancer diagnosis. In a population of patients already known to have an increased risk of shingles, this study highlights the important role of CMI in protecting against shingles.6

References

  1. Weinberg A and Levin MJ. VZV T cell-mediated immunity. Curr Top Microbiol Immunol 2010;342:341-357.
  2. Oxman MN. Herpes zoster pathogenesis and cell-mediated immunity and immunosenescence. J Am Osteopath Assoc 2009;109(6 Suppl 2):S13-S17.
  3. Marra F et al. Risk factors for herpes zoster infection: A meta-analysis. Open Forum Infect Dis 2020;7:ofaa005.
  4. Arnold N and Messaoudi I. Herpes zoster and the search for an effective vaccine. Clin Exp Immunol 2017;187:82-92.
  5. Laing KJ et al. Immunobiology of varicella-zoster virus infection. J Infect Dis 2018;218(Suppl 2):S68-S74.
  6. Qian J et al. Risk of herpes zoster prior to and following cancer diagnosis and treatment: A population-based prospective cohort study. J Infect Dis 2019;220:3-11.

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July 2024 | NP-GB-HZU-WCNT-240015 (V1.0)