In brief (March 2015, part I): immune variability and HPV vaccine

Two picks from what I’ve read over the past couple of months:
the adaptability of the immune system, or how our immune system is more heavily shaped by our environment and the microbes we encounter than by our genes,
HPV vaccine safety profile, or how a nationwide study conducted in Sweden and Denmark found no increased risk of developing multiple sclerosis or other demyelinating diseases following quadrivalent HPV vaccination.

  • The adaptability of our immune system

There is considerable variability among the immune systems of humans. For example, the numbers of different immune cell types circulating in the blood may vary a lot from one individual to the other – even while staying within the range of what is usually found in healthy people. Although both genetic and environmental factors contribute to this variability, it is difficult to estimate how much each contributes to shaping the immune system. A recent study has now found evidence that much of the variation observed in the human immune system is attributable to non-heritable influences. In other words, the environment in which we live and with which we interact seems to play a more important role in shaping our immune system than the genes we inherit from our parents.

To assess the influence of heritable (genetic) and non-heritable (environmental) factors on the immune system, the researchers enrolled 210 twins in their study: 78 pairs of monozygotic (identical) twins and 27 pairs of dizygotic (fraternal) twins. They then collected data on a large number of immune parameters, most of them related to the adaptive arm of the immune system: numbers of different immune cell types present in the blood, levels of serum proteins (cytokines, chemokines, growth factors), and responses of immune cells to different types of in vitro stimulation. They found that these parameters varied among individuals mainly as a consequence of non-heritable factors, with heritable factors having only a limited influence. The differences between the immune systems of older monozygotic twins were larger than those found between the immune systems of younger ones, highlighting how the impact of environmental factors on the immune system increases over time. The researchers also compared pairs of monozygotic twins who had never been infected by CMV (cytomegalovirus) to pairs who were discordant for CMV infection (one twin infected, the other not). They found that exposure to CMV influenced more than half of the parameters studied, and that identical twins with different infection statuses had more divergent immune systems than twins who were both uninfected.

Altogether, the authors of the study suggest that the cumulative influence of environmental factors, and especially the microbes we encounter, modulate the shape of our immune system over time, eventually outweighing the impact that most heritable factors may have on shaping our immune system.

(Brodin et al. Cell 15 January 2015. doi: 10.1016/j.cell.2014.12.020)

  • HPV vaccine safety profile

The quadrivalent human papillomavirus (qHPV) vaccine was licensed in 2006, and since then many countries and the World Health Organization have recommended that girls and young women should receive the vaccine (the reason being that HPV is the main cause of cervical cancer). Case reports of vaccinees developing multiple sclerosis or other demyelinating diseases have raised concerns about the safety of the vaccine in some countries, especially among the general public as such cases were widely advertised by social and news media in these countries. However, there was no indication whether these case reports represented a true increase in the risk of developing a demyelinating disease after HPV vaccination, or whether they merely reflected the background incidence rate of such diseases in girls and young women in general.

A study conducted in Sweden and Denmark has now gathered evidence to answer that question and found no association between qHPV vaccine and development of multiple sclerosis or other demyelinating disease of the central nervous system. The study, based on nationwide population registers, included almost 4 million women (aged 10-44), among whom about 800,000 were vaccinated. The population-based cohort was followed up from 2006 to 2013, and information on qHPV vaccination and incident diagnoses of multiple sclerosis or other demyelinating disease was collected. Analysis revealed no increased risk of developing a demyelinating disease in a 2-year period following qHPV vaccination. Four alternative risk windows were also explored (0-6 months, 6-12 months, 1-2 years, and more than 2 years after vaccination), yielding similar results.

(Scheller et al. JAMA 6 January 2015. doi: 10.1001/jama.2014.16946)


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