Rethinking definitions of autoimmune disease

Why autoimmune diseases should be redefined by molecular pathway

By Lauren Martz, senior writer

 

The autoimmune field is dialing up its search for better biomarkers as it seeks to make the next step change from the targeted therapiesthat overtook blanket immunosuppressants. The question is whether autoimmunity might follow the lead of oncology and classify indications by molecular drivers rather than the symptoms or tissues involved... (read the full article).

 

From Biocentury Innovations

My coauthors

Meet the lab: Team Schlenner

Meet the lab: Team Humblet-Baron

The employer-mentor tension

I've been reading a lot on the movement to normalise the working conditions of a PhD. A PhD is a lifestyle choice more than a job. The work permeates into your evenings, weekends and holidays. It is difficult to mentally dissociate from the work due to the emotional investment placed in it, which frequently leads to mental health issues. A growing number of students want the PhD to become a more normal "9-5" job, to work just the standard hours they are paid for, in conditions similar to any other profession. This is entirely reasonable.

At the same time, I am seeing a great desire for personal mentoring of students. Professors should be more than a scientific advisor; they should be a coach, a mentor, a career guide and a cheerleader. In this regard, the Professor is much more than a simple employer. This is also entirely reasonable.

Are these two goals, each reasonable in their own right, compatible? To me they pull me in opposite directions. If I support the student's right to be a normal employee, isn't the natural corollary the right to be a normal employer? If I make a point of not intruding on my student's home time, surely I have the right to not let my students intrude on my home time? 

There are two additional asymmetries to consider. First, the asymmetry in power. An email from the Professor to the student on holiday is more invasive then the reverse, due to the nature of the relationship. I am training myself not to send emails on the weekend (my prime thinking time), because even though I intend them to be read on Monday, my students may feel obliged to read them on the weekend. The second asymmetry is less well recognised, the asymmetry in numbers. The student has one professor, while the professor has many staff. I have 20 staff and students, and more than 100 ex-lab members. While weekend-disrupting problems are rare individually, there is at least one every weekend. With HR, each person may only have a work-altering personal problem once every two years, but the net effect is that I deal with such a matter on a monthly basis. 

My personal solution to the tension inherent in the employer-mentor balance is to allow my students and staff to pick their own place on that continuum, but their choice impacts both of our roles. If a student wants to work as a normal employee and not take their job home then they can, but equally they don't get the right to then intrude on my home. It is just not fair for a student to miss deadline after deadline on a piece of writing I assign them, but then to expect me to urgently proof-read their (late) progress report on Sunday afternoon. For a student who has worked above and beyond I will take their thesis draft with me on holiday if need be, but only because we both are invested. A student who doesn't go to the departmental seminars doesn't earn the right to get a paid trip to an international conference. The student who is creative and innovative in pushing technical boundaries will get support in new kit and training. A student who is passionate and talented in research will literally get a hundred hours in career development mentoring from me, but I am reluctant to invest more than 10 minutes doing the same for a student who refuses to be a team member.

In theory, I am comfortable with this choice. In practice it is difficult for me to maintain. Far too often it is the staff who give and give to those around them that are the least likely to ask in return. By contrast, toxic staff (fortunately I have none now!) expect mountains to be moved for them. I know my own nature, and unfortunately I am too much of a workaholic and care too much about my work to act as a completely impartial employer. Management style will always be a work in progress, constantly evolving with my own growth and in response to my staff.

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Wednesday

Oct312018

Meet the lab: Team Babraham

Wednesday, October 31, 2018 at 9:46AM

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tagged Liston lab

Monday

Oct292018

Meet the lab: Team Neuroimmunology

Monday, October 29, 2018 at 9:57AM

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tagged Liston lab

Thursday

Oct182018

Research connects psychological factors and the immune system

Thursday, October 18, 2018 at 1:10PM

Menzies Foundation: The following story is from our publication Taking the lead: 40 stories of impact. 

Professor Adrian Liston is leading the way in immunology research overseas. He was awarded the 2006 NHMRC Menzies Fellowship, which allowed him to work at internationally-renowned labs through the University of Washington in Seattle, where he continued his groundbreaking research into controlling immune activation. He now runs his own lab in Belgium, where he works on solutions for patients with rare immune disorders that pharmaceutical companies don’t investigate. He simultaneously works on trying to understand why the regulatory cells actually work, and what’s different about these cells when they’re in different organs.

Since establishing his lab, Prof Liston and his team have made regular noteworthy findings, including one that links mental health with the immune system. He was able to ‘seize the moment’ and test a hypothesis from a ‘natural experiment’ during an outbreak of gastro that occurred when the water system was accidentally contaminated in two small towns outside Antwerp.

“The hypothesis linking mental health with the immune system had been tested successfully on mice,” Prof Liston explains. “But it hadn’t been tested on humans. It’s only because we were able to take advantage of this experiment of nature—the synchronised infections— that we were able to test the hypothesis.

"Our testing showed that individuals who had high levels of depression at the time of the infection had a different immune response to those who didn’t. The results showed that the depression-immunity link wasn’t something in the mind, it is due to actual changes in the blood that gives depressed or anxious people a different immune system response.

"Even years later, among people whose mental health had improved since that original time of infection, they still had ongoing complications because they got hit with an infection at a point where they had a lot of depression or anxiety.” 

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tagged Liston lab

Tuesday

Oct162018

Golden Pipette won by Dr Carly Whyte

Tuesday, October 16, 2018 at 3:39PM

Congratulations to Dr Carly Whyte, for winning the Golden Pipette!

Carly won the Golden Pipette for her mind-boggling data on how the cellular source of IL-2 profoundly alters the impact of this key cytokine on the cells around it. Data to be published, as soon as we understand it!

Carly will be moving over to the Babraham in January. Will the Golden Pipette be won back by team Leuven in time? Or will Cambridge take ownership of this proud trophy?  

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tagged Golden Pipette, immunology

Tuesday

Oct162018

Our immune systems are incredibly diverse. How much of that diversity is due to our genes?

Tuesday, October 16, 2018 at 2:38PM

Each of our immune systems acts a little bit differently. Environmental factors have an impact, but so do our genes. A team of researchers in Leuven went looking for links between more than 10 million genetic variations and more than 50 immunological traits. Their findings help to explain why some people have a higher risk for immune diseases than others.

Our immune systems are molded by our unique genetic make-up. Add to that a complex mix of environmental drivers, and you get an enormous functional diversity. From an evolutionary point of view, this diversity is essential to minimize the chance that a pathogen could wipe out an entire population.

But the flip-side is that we’re also greatly diverse when it comes to susceptibility or resistance to a broad range of diseases – not only those with an obvious immunological component, such as autoimmunity, allergy, inflammation and cancer, but also those with a more indirect link to immune-deregulation, such as cardiovascular, metabolic and neurological diseases.

A genome-wide survey

While scientists have studied the links between genetic variations and a whole range of different diseases, the characterization of this “genotype-phenotype relationship” for the immune system itself has received far less attention.

That is why a team of scientists led by An Goris (KU Leuven) and Adrian Liston (VIB-KU Leuven) undertook a large genetic study with almost 500 participants. In a so-called genome-wide association study, or GWAS, they probed more than 10 million genetic variations, spread out across the genome, for links to 54 different traits relevant to adaptive immunity. This allowed the researchers to determine which genetic variants were, for example, typical for people with high or low levels of different pro- or anti-inflammatory cytokines.

“We found eight previously unknown associations,” says An Goris, lead geneticist of the study. “The strongest connection was for a genetic variant present in only 2% of the study participants.” All of the identified genetic associations provide important biological insights into what drives variation in our immune systems.

This is only the tip of the iceberg, according to Goris: “What we know now, explains about 10% of the variation, but we are still in the initial discovery phase. There might be many more genetic variants—including relatively rare ones—that affect our immune response and thus our susceptibility to certain diseases.”

Helping to map disease risk and refine treatment

Mapping how genetic variants affect immune function will not only help us understand disease mechanism better, it should also help to refine treatment options.

“The clearest example is the clinical implication offered by genetic variation in the RICTOR gene,” explains Adrian Liston, lead immunologist on the study. “We now know that RICTOR changes the production of a cytokine called IL-4, providing a new therapeutic target for treatment of autoimmune diseases and asthma.”

In many cases, the effects are more subtle and indirect, adds Liston: “Most people will carry dozens of genetic variants that may skew the immune system in a particular direction. This accounts for part of the reason why different people have different risks for immune diseases, but we are much more than the sum of our genes.”

—

Lagou et al. 2018 Cell Reports. 'Genetic architecture of adaptive immune system identifies key immune regulators'.

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tagged Liston lab, genetics, immunology

Meet the lab: Team Babraham

Meet the lab: Team Neuroimmunology

Research connects psychological factors and the immune system

Menzies Foundation: The following story is from our publication Taking the lead: 40 stories of impact. 

Professor Adrian Liston is leading the way in immunology research overseas. He was awarded the 2006 NHMRC Menzies Fellowship, which allowed him to work at internationally-renowned labs through the University of Washington in Seattle, where he continued his groundbreaking research into controlling immune activation. He now runs his own lab in Belgium, where he works on solutions for patients with rare immune disorders that pharmaceutical companies don’t investigate. He simultaneously works on trying to understand why the regulatory cells actually work, and what’s different about these cells when they’re in different organs.

Since establishing his lab, Prof Liston and his team have made regular noteworthy findings, including one that links mental health with the immune system. He was able to ‘seize the moment’ and test a hypothesis from a ‘natural experiment’ during an outbreak of gastro that occurred when the water system was accidentally contaminated in two small towns outside Antwerp.

“The hypothesis linking mental health with the immune system had been tested successfully on mice,” Prof Liston explains. “But it hadn’t been tested on humans. It’s only because we were able to take advantage of this experiment of nature—the synchronised infections— that we were able to test the hypothesis.

"Our testing showed that individuals who had high levels of depression at the time of the infection had a different immune response to those who didn’t. The results showed that the depression-immunity link wasn’t something in the mind, it is due to actual changes in the blood that gives depressed or anxious people a different immune system response.

"Even years later, among people whose mental health had improved since that original time of infection, they still had ongoing complications because they got hit with an infection at a point where they had a lot of depression or anxiety.” 

Golden Pipette won by Dr Carly Whyte

Congratulations to Dr Carly Whyte, for winning the Golden Pipette!

Carly won the Golden Pipette for her mind-boggling data on how the cellular source of IL-2 profoundly alters the impact of this key cytokine on the cells around it. Data to be published, as soon as we understand it!

Carly will be moving over to the Babraham in January. Will the Golden Pipette be won back by team Leuven in time? Or will Cambridge take ownership of this proud trophy?  

Our immune systems are incredibly diverse. How much of that diversity is due to our genes?

Each of our immune systems acts a little bit differently. Environmental factors have an impact, but so do our genes. A team of researchers in Leuven went looking for links between more than 10 million genetic variations and more than 50 immunological traits. Their findings help to explain why some people have a higher risk for immune diseases than others.

Our immune systems are molded by our unique genetic make-up. Add to that a complex mix of environmental drivers, and you get an enormous functional diversity. From an evolutionary point of view, this diversity is essential to minimize the chance that a pathogen could wipe out an entire population.

But the flip-side is that we’re also greatly diverse when it comes to susceptibility or resistance to a broad range of diseases – not only those with an obvious immunological component, such as autoimmunity, allergy, inflammation and cancer, but also those with a more indirect link to immune-deregulation, such as cardiovascular, metabolic and neurological diseases.

A genome-wide survey

While scientists have studied the links between genetic variations and a whole range of different diseases, the characterization of this “genotype-phenotype relationship” for the immune system itself has received far less attention.

That is why a team of scientists led by An Goris (KU Leuven) and Adrian Liston (VIB-KU Leuven) undertook a large genetic study with almost 500 participants. In a so-called genome-wide association study, or GWAS, they probed more than 10 million genetic variations, spread out across the genome, for links to 54 different traits relevant to adaptive immunity. This allowed the researchers to determine which genetic variants were, for example, typical for people with high or low levels of different pro- or anti-inflammatory cytokines.

“We found eight previously unknown associations,” says An Goris, lead geneticist of the study. “The strongest connection was for a genetic variant present in only 2% of the study participants.” All of the identified genetic associations provide important biological insights into what drives variation in our immune systems.

This is only the tip of the iceberg, according to Goris: “What we know now, explains about 10% of the variation, but we are still in the initial discovery phase. There might be many more genetic variants—including relatively rare ones—that affect our immune response and thus our susceptibility to certain diseases.”

Helping to map disease risk and refine treatment

Mapping how genetic variants affect immune function will not only help us understand disease mechanism better, it should also help to refine treatment options.

“The clearest example is the clinical implication offered by genetic variation in the RICTOR gene,” explains Adrian Liston, lead immunologist on the study. “We now know that RICTOR changes the production of a cytokine called IL-4, providing a new therapeutic target for treatment of autoimmune diseases and asthma.”

In many cases, the effects are more subtle and indirect, adds Liston: “Most people will carry dozens of genetic variants that may skew the immune system in a particular direction. This accounts for part of the reason why different people have different risks for immune diseases, but we are much more than the sum of our genes.”

—

Lagou et al. 2018 Cell Reports. 'Genetic architecture of adaptive immune system identifies key immune regulators'.