Share a child? Then your immune systems look pretty similar too

The human immune system is shaped by family and household

Raising a child together has a greater effect on your immune system than the seasonal 'flu vaccine or travellers' gastroenteritis, a study by researchers at the VIB in Belgium and the Babraham Institute in the UK has found.

The research took a detailed look at the immune systems of 670 people, ranging from 2-86 years of age, to understand more about what drives variation in our immune systems between individuals. From an assessment of the effects of a range of factors, including age, gender and obesity, one of the most potent factors that altered an individual's immune system was whether they co-parented a child. Individuals who lived together and shared a child showed a 50% reduction in the variation between their two immune systems, compared with the diversity seen in the wider population. 

Dr Adrian Liston, a researcher at the VIB and University of Leuven who co-led the research said: "This is the first time anyone has looked at the immune profiles of two unrelated individuals in a close relationship. Since parenting is one of the most severe environmental challenges anyone willingly puts themselves through, it makes sense that it radically rewires the immune system - still, it was a surprise that having kids was a much more potent immune challenge than severe gasteroenteritis. That's at least something for prospective parents to consider - the sleep deprivation, stress, chronic infections and all the other challenges of parenting does more to our body than just gives us grey hairs. I think that any parents of a nursery- or school-age child can appreciate the effect a child has on your immune system!"

Every individual has a unique immune system, something which can be visualised as a unique location in “immunological space”. Our immune systems are also dynamic, with minor differences on a day-to-day basis. The biggest shapers of our immune systems are age, with a gradual ageing of the immune system over time, and cohabitation, where having a child together causes the unique immune signature of each individual to come much closer. Image produced by Dr Carl 

Participants in the study were assessed over a period of three years. Regularly monitoring their immune systems showed that the individuals maintained a stable immune landscape over time, even after their immune systems were triggered into action by the seasonal ‘flu vaccine or gastroenteritis. The researchers found that following immune challenge, our immune systems tend to bounce back to the original steady state, demonstrating the elastic potential of our immune system.

In assessing the effect of other factors on the immune system, such as age, obesity, gender, anxiety and depression, the study found that age is a crucial factor in shaping the immunological landscape, agreeing with the age-related decline seen in response to vaccination and reduced resistance to infection.

Dr Michelle Linterman, a researcher at the Babraham Institute who co-led the research said: “Our research shows that we all have a stable immune landscape which is robustly maintained. What is different between individuals is what our individual immune systems look like. We know that only a small part of this is due to genetics. Our study has shown that age is a major influence on what our immune landscapes look like, which is probably one of the reasons why there is a declining response to vaccination and reduced resistance to infection in older persons.”

The research is published by the leading international journal Nature Immunology and was funded by two European Research Council grants. Dr Michelle Linterman and her group at the Babraham Institute are supported by the Biotechnology and Biological Sciences Research Council.  Dr Adrian Liston and his group are members of the VIB and University of Leuven, in Belgium.

Publication: Carr et al. (2016) The human immune system is robustly maintained in multiple equilibriums by age and cohabitation. Nature Immunology

Does it take too long to publish research?

This is the question posed by Nature this week. The article is full of stories of research papers submitted to Science and then finally accepted two years later in PLoS One. Certainly I've had experiences pretty close to that, and for big stories from my lab about a year between submission and acceptance is normal. At Nature, the median time between acceptance and publication is 150 days (up from 85 days a decade ago). Even more striking is the amount of data needed to get into Nature - a 10-fold increase in data panels (and each panel has a lot more information too!).

The big problem is not really the dozens of experiments needed to reply to reviewers though. Rather, I think the hardest part is the roulette of getting editors/reviewers that like the paper. The article is rather dismissive of "journal shopping", but the simple fact is that submitting a paper is a lot like rolling the dice. 95% of articles that I have published have ended up in a journal of similar rank to the initial submission (the other 5% cause most of the heart-ache). But this doesn't mean that there is a smooth ride. Rather, you can spend a year at review at Cell, doing all the experiments those reviewers want, then you still get rejected. The paper gets rejected at Immunity without review, then Nature Medicine sends it out but gives you new reviewers who want an entirely different set of experiments. No matter how much you have done, the big journals will always ask for more - and you can't predict in advance what they will ask.

All of this takes a lot of time, however having published in the social sciences as well, they are even slower. The difference is in how much effort and energy the publication process takes in medicine. At a top journal, it is not unusual for the revision to require €100,000 in salary and reagents to get those last experiments done for the reviewer. To me, the more important question is whether this cost is worth it.

School outreach

Many thanks to Annemarie, Dean and Evelyne for inspiring the next generation of scientists!

Journal club: Patient diagnosed with non-human cancer

In a fascinating case report in the New England Journal of Medicine, Muehlenbachs et al identified a patient with disseminated cancer through the lungs and lymph nodes. The major oddity of the cancer was the small size of the cells, far smaller than human cells, indicating that the cancer cells were non-human. Extensive analysis identified the cancer cells as coming from Hymenolepis nana, the dwarf tapeworm. The patient was infected with tapeworms, one of which developed cancer (as can happen to any organism). These tapeworm cancer cells then metasized from the tapeworm into the host, adapted to the host and spread throughout the body as a foreign cancer. While the immune system is normally highly effective at clearing foreign organisms from the body, the tapeworm cancer cells were able to survive and disseminate throughout the body, possible for a combination of three reasons: i) tapeworms induce immune tolerance against their antigens, ii) the tumour cells were selected to be of low immunogenicity, and iii) the patient was HIV+ and immunodeficient. While this may be a one-off case, since parasite infections are so common perhaps we will find non-human cancers in other patients?

Muehlenbachs et al. 'Malignant Transformation of Hymenolepis nana in a Human Host'. New England Journal of Medicine. 2015. 373:1845

Ebastine provides relief from Irritable Bowel Syndrome

In a study published today by Gastroenterology, we demonstrate in a randomized placebo controlled trial that the anti-histimine Ebastine provides relief from the symptoms of Irritable Bowel Syndrome (IBS). The study, led by Prof Guy Boeckxstaens and in collaboration with the Translational Immunology Laboratory, tested the effect of Ebastine on pain relief. Over a 12 week course, nearly 50% of IBS patients showed considerable relief from symptoms. As Ebastine is a safe over-the-counter anti-histimine, commonly prescribed for allergy, this study could be rapidly extended to millions of IBS patients across the world.

Read more: Wouters et al. 'Histamine Receptor H1-mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome'. Gastroenterology. 2016

Francqui Chair award

Women in science

This is one of the best articles I have read on the topic. Not enough women in top-level positions? The solution is simple - just hire more women. No more blathering on about childcare and maternity leave, just hire women. 

As the mother of two amazing women, I would say that family issues are the least of the problem ... It has been shown that women without children generally do not advance any faster or further than women with families. In their ground-breaking 2002 paper, 'Do Babies Matter', researchers Mary Ann Mason and Marc Goulden showed that women with children who remain in full-time academia are no worse off than women without children. Both groups lag well behind men — especially men with children, who lead everyone else.

...

When I give a colloquium at a university whose physics department lacks female faculty members, I often ask: “Have you thought about hiring women?” The answer is usually earnest: “Oh yes, we definitely want to do that, but we want to hire the best.” Do my hosts realize how insulting it is to imply those two goals are mutually exclusive? ... As I (and many others) have pointed out several times, the failure to hire women and minorities in science is a guarantee that the best are not being hired.

European Research Council funding for the laboratory

VIB press release:

The European Research Council (ERC) has awarded 4 VIB scientists a consolidator grant: Kevin Verstrepen (VIB/KU Leuven), Adrian Liston (VIB/KU Leuven), Mohamed Lamkanfi (VIB/UGent) and Daniël Van Damme (VIB/UGent). These 'consolidator grants' are rewarded to scientists (PhD 7-12 years) who already showed that they are able to run their own lab. The European Research Council's grant allows them to anchor the start of a high risk/high gain program, feasible through this recognition of nearly 2 Mio€ per scientist.

ERC grants
Right from the start, VIB recognized the importance of ERC for its own mission, given our obvious synergy at the science policy level:
- Frontier research
- Excellence as the only selection criterion
- Bottom-up, all fields
- Support for the individual scientist
- International peer review

Every year VIB encourages group leaders to apply for  ERC grants and supports them when they do. With these four new ERC grants VIB has reached the impressive number of 34 ERC-grants.

Recognition for four VIB researchers

Adrian Liston (VIB/KU Leuven) who will develop new molecular tools to study the immune system in the brain during neurodegenerative disease, says: “This ERC grant offers me an exciting opportunity to start a major initiative in looking at the interaction between the immune system and the brain.”

Kevin Verstrepen (VIB/KU Leuven) will investigate whether cells can somehow remember past experiences, and whether such past experiences influence how cells respond to their current environment.  In other words, he wants to find out whether living cells, including simple cells such as microbes as well as more complex cells in animals, have a basic form of memory (that is obviously more simple and restricted from the kind of memory associated with a brain in higher animals and humans). His reaction: “The ERC funding provides a fantastic boost to our research, because the amount of money we receive from Europe is substantial enough to recruit a complete team of scientists to pursue a new line of research that really pushes the boundaries of our current knowledge of biology.”  

Mo Lamkanfi (VIB/UGent): ‘Our ERC project will map the broad communication between inflammasomes and the diverse programmed cell death mechanisms in immune cells. This will help to define novel approaches to treat autoinflammatory and -immune diseases by converting pathological cell death into non-inflammatory responses.’

Daniël Van Damme (VIB/UGent): “Achieving an ERC grant consolidates my independent research position within the VIB Department of Plant Systems Biology and Ghent University. It provides me with the means to unravel why the process of endocytosis evolved differently in plants compared to animal and yeast cells.” With his T-REX project he will combine ultrastructural analysis of the main endocytic adaptor complex in plants with proteomic identification of its endocytic cargo and functional cell biological analysis of its subunits.

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If anyone is interested in my advice on applying for ERC grants, here are the hints I wrote in 2010 after going through the ERC Start grant process.