SISTEMAS DE DISTRIBUCIÓN
1.13 CURVAS CARACTERÍSTICAS DEL MOTOR (MEP).
As described in the introduction, zoster reactivation occurs due to a waning of VZV-specific T cell-mediated immunity. Below is some biological evidence suggesting that the exposures of interest (specifically, RA, SLE, IBD, asthma, COPD, depression, diabetes, and CKD) investigated as risk factors for zoster in this thesis, are associated with impaired cell-mediated immune function.
Autoimmune conditions
Autoimmune conditions are associated with increased risk of infections,136 indicating poor
immune function. Cell-mediated immunity may be suppressed in patients with autoimmune conditions, due to the routine use of immunosuppressive medications, or the underlying
disease itself.136 RA patients have been shown to experience accelerated immune senescence
of T cells and reduced T cell diversity.137 A study of 38 SLE patients and 51 healthy controls,
found decreased cellular immune responses and VZV-specific immunity in the SLE patients compared to healthy controls, and this was not influenced by immunosuppressive medication
use.138 This finding suggests that SLE, as a disease, may be driving impaired cell-mediated
immune function. The other autoimmune condition assessed in this thesis is IBD. Little research exists exploring VZV-specific immunity among IBD patients, however IBD is reported
to be associated with abnormalities in cell-mediated immunity.58,139
Asthma and chronic obstructive pulmonary disorder
Authors have suggested that asthma might play a role in waning cell-mediated immunity, as evidenced by reduced immune response to measles, mumps and rubella vaccination in
asthmatic compared to non-asthmatic children.140 It is currently unclear whether COPD as a
disease itself alters cell-mediated immunity; however, some authors have suggested that
COPD leads to systemic immune disturbances.141 As asthma and COPD are both treated with
corticosteroids, patients may experience drug-induced alterations in cell-mediated immunity from use of ICS142-146 and oral corticosteroids.104
Depression
Depression may also lead to poorer cell-mediated immune function. Recent virology studies indirectly support the hypothesis that depression may lead to an increased risk of zoster. A
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study demonstrated that 52 patients with major depressive disorder had lower VZV-specific cell-mediated immunity, compared to 52 age and sex-matched patients without depression,
and the level of the immune response correlated negatively with the severity of depression.147
Another study showed that depressed individuals had reduced VZV cell-mediated immune
responses when administered the zoster vaccine.148
There is also evidence that stress, common in patients with depression, may also affect cell- mediated immunity. The central nervous, endocrine and immune system interact with each other, such that a dysregulation in one system can have an effect on the other systems. Stress can affect a number of neuroendocrine functions, including activating the hypothalamic–
pituitary–adrenal axis which can thereby in turn affect cell-mediated immunity.149,150
Additionally, patients experiencing stress are likely to have habits, such as reduced sleep, which may indirectly affect immune function. Virological evidence that astronauts have experienced sub-clinical VZV reactivation during space travel, suggests stress may trigger a
reduced cell-meditated immune response.151,152 Finally, evidence of a randomised controlled
trial of a stress-reducing behavioural intervention, Tai Chi, found the Tai Chi group showed higher levels of VZV cell-mediated immunity than the control group (who received some health
education) after 25 weeks.153
Chronic Kidney Disease
Researchers have suggested that a decline in renal function can result in reduced cell- mediated immunity. VZV-specific cell-mediated immunity has not been assessed in patients with kidney disease. However, patients with CKD demonstrate an increased susceptibility to infections (the second most common cause of death in dialysis patients is infection) and decreased serological response to vaccination, such as Hepatitis B and influenza, which points
to an impaired cellular immune response.154,155 There is also some evidence that CKD causes a
diminished activation of T cells.156 The causes of immune dysfunction in CKD are not fully
understood, however uraemia (a raised level of waste products in the blood, usually
eliminated by the kidneys), is thought to be the mediating factor.157
Diabetes
Patients with diabetes have more infections than patients without diabetes158 and
hyperglycaemia (too much blood sugar in the bloodstream) is believed to lead to immune
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specific cell-mediated immune responses were reduced in patients with diabetes, compared to healthy controls.162
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4.7. Chapter summary
Quantification of risk factors for herpes zoster
Current zoster vaccination campaigns focus on older people only. Recent literature has suggested that a range of clinical conditions are
associated with an increased risk of zoster, raising the possibility that some younger people may be at high risk. However, large, highly powered studies investigating the association of these clinical conditions with zoster are lacking. A case-control study was carried out in CPRD with 144,959 zoster cases and
549,336 age, sex and practice-matched controls, and the associations between a range of potential risk factors and zoster were investigated.
Conditions associated with increased risk of zoster included RA, SLE, IBD, COPD, asthma, CKD, type 1 diabetes and depression.
The increased risks were generally greater among younger age groups. Those at highest risk of zoster remain those who have severely weakened
immune systems and the current vaccine is contraindicated for these individuals. This emphasises that alternative strategies (which could include non-live vaccines and antiviral prophylaxis) are needed to reduce the risk of shingles among these patient groups.
Further information about the risk of complications, particularly PHN, is needed to decide if it is cost-effective to vaccinate certain patients.
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