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Genetics and Autoimmunity

by | Oct 26, 2018 | Autoimmune, Autoimmune Disease, Functional Medicine

Genetics and Autoimmunity

Welcome to video three in the series on autoimmune disease. This presentation is on genetics and autoimmunity. I’m Robyn Puglia, nutritional therapist and certified functional medicine practitioner.

Developing Autoimmune Disease

In order to develop autoimmune disease, it is generally considered that you need to have three variables in place. You need to have barrier permeability which leads to immune system dysregulation, and that can be the gut. It can be the skin, it can be the lungs, um, and a barrier permeability essentially creates inflammation in the body and changes the way the immune system works. So that’s factor number one. Factor number two is it’s considered you need to have the genetic predisposition to develop autoimmunity in the first place. And of course that’s what we’re going to be talking about today.

And lastly, you need to have some kind of environmental trigger and usually we’re talking about a toxin or a bacteria or a virus. It can be a food, it can be stress in some instances. But today, as I said, we’re going to be talking about genetics and the role that genes play.

Both genetic and environmental factors play a role in the development of autoimmune disease, but from a scientific perspective, the importance of genes became obvious when it was noticed that the risk of autoimmunity was increased in twins and siblings of affected individuals. Okay.

So common sense and simple observation of affected families allows us to understand that there’s a genetic component to autoimmunity. This of course was really exciting for the scientific community because if you can find the gene responsible, then you might be able to find a way to switch it off and to cure the disease.

Unfortunately, it turns out that it’s just not that simple. So let’s look at some of the genetic information and please bear in mind that I’m trying to keep this really simple. So firstly I would like to talk about what’s called HLA typing.

Genetic Variability

A large part of the research around genetics and autoimmunity relates to this genetic variable. HLA stands for human leukocyte antigen and there is a fairly strong connection between variations in the HLA regions of the genes and Autoimmunity.

I think it’s really important to understand, and for me to say this at this point, that HLA typing is not diagnostic, but it is used to understand association and sometimes is used to rule in or rule out autoimmune disease.

So what exactly is HLA? So the HLA system is the genetic system that codes for major histocompatibility complex proteins in the human immune system. And MHC proteins help to regulate the immune system. And in fact, I talked about this a lot on in video 2 of this series, so if this is starting to get confusing, then I recommend that you watch the second video on how the immune system works. I talk about the importance of MHC proteins and how they work with antigen presentation in, in the immune system.

The HLA system and MHC Proteins

So the HLA system is the system of genes that tells the body how to make these MHC proteins. And the MHC proteins are really, really important because they help us to regulate the way that our immune system works in response to environmental stimuli. They help us to understand when we need to be responding to something , specifically an external variable. So the HLA genes then have got a lot of variance because this allows them to fine tune the adaptive immune system responses. HLA A,B and C correspond to MHC class one antigen presentation and they present proteins from inside the cell to killer T-cells. So for example, if the cell is infected by a virus, the way that our immune system is capable of responding to that is that the MHC protein samples of the viral protein inside the cell and it creates a kind of a billboard to show it on the outside of the cell so that your immune system recognizes there’s a problem in that cell that needs a response, and will likely destroy this infected cell. And then HLA-D corresponds to MHC class two. They present antigens from outside the cell to the T-helper cells and T-helper cells stimulate antibody producing B cells. And of course antibodies are a cornerstone of autoimmunity and immune function. So HLA-D corresponds to coeliac disease because of course gluten is presented from outside the cell.

So what does that all mean exactly? I’m so it means that you don’t really have a gene that gives you an autoimmune disease. I think that this is a really important thing to understand that the genes that predispose you to autoimmunity or that increase your risk of developing autoimmunity are not for an auto immune disease. They are  the genes that affect the way that your immune system responds to environmental stimuli such as infection.

And I think that that is a really critical thing for you to understand. It’s not a gene for autoimmunity. It’s a gene that changes the way that your body responds and how your immune system response if you have a virus or if you are exposed to a bacteria or another environmental antigen.

So, HLA-DQ2 and DQ8 are associated with Coeliac disease. And we know that this means it’s a different form of the MHC class 2 antigen presentation system. HLA DR3 is associated with type one diabetes, autoimmune, hepatitis, Lupus, and Sjogren’s. HLA DR4  is associated with rheumatoid arthritis and Type one diabetes.

Susceptibility to Autoimmune Disease

But now we are starting to see, in the research some associations in the HLA associated with MHC class. So we see Hlab 27 associated with ankylosing spondylitis and in fact there is a fairly also well understood infectious association with ankylosing spondylitis that involves the gut and Klebsiella. And we are starting to see some of the HLA B and C types associated also with type one diabetes with multiple sclerosis, and with Graves’ disease. And I think that this suggests a very strong role for infection specifically for viral involvement in the initiation of those diseases. And of course that is something that naturopathic medicine, alternative medicine, nutritional therapy have been saying for a really long time, so this is not actually such a big surprise for a lot of people, especially if they’re in clinical practice.

But it great that it helps us to understand more about why certain people are more susceptible. So for example, everybody has Epstein Barr virus. Why are some people more susceptible to developing autoimmune disease when they have Epstein Barr virus onboard? Partially, that’s to do with the genes that they have that tell the body how to respond to a virus.

Okay. So it’s more complicated than just do you have the gene because 35 percent of the population have the gene for celiac disease, for example, and only one to two percent have actual celiac disease. And then around two percent of those who have been diagnosed with celiac disease don’t actually necessarily have the gene for it. So it’s not quite as simple as single gene.

There are genes that predispose you to hyper response of the immune system: to generally being proinflammatory in the presence of certain environmental factors.

There are genes that make you more susceptible to infection.

There are genes that make you more susceptible to toxic exposures. You know, you might have very poor glutathione levels and therefore more oxidative stress. And we know that oxidative stress is a variable that’s associated with increased prevalence of autoimmune disease such as Lupus.

You know, you might have a combination of more than one of those genes. And of course that then makes you very susceptible to developing problems. In the Western world where we have so many environmental triggers that just throughout our everyday life, we have stress, we have oxidative stress, we’ve got chemicals in the home, we’ve got processed foods. So when you have a combination of the genes and combination of environmental factors, you might just be at higher risk.

And on top of all of that, now we have, when we’re talking about genes or there is something called a Single Nucleotide Polymorphism, which is also known as a snip or also known as a gene variant.

And this is where there are lots of shades of grey that starts to become involved.


Ok, so a gene is basically a recipe for a protein. A protein is a string of amino acids. So it’s like a word that is spelled with up to several hundred letters. So you can see here in the slide that here’s a piece of a protein and it’s a string of letters, that’s how it’s coded.

And the gene is telling your body how to spell that word and with that information, that’s how your body assembles the protein. So with a snip, with a single nucleotide polymorphism, you are replacing one letter with another letter.

So in this example, in this little cartoon here, we’re replacing the G with the C or vice versa. They’re interchangeable in this scenario, and this might have no effect. There are lots of snips that we can have in the body, so this might have no effect, but it might also change the way that the protein functions at the end of that process. And some of this information is known to us. Like I said, sometimes we understand that if you have a snip in this area that the end result of that will be a change in the way that your body works. But we don’t really know it all. Each of us has more than a million snips, and we don’t know what they all do, and we don’t know what happens with each combination of snips that is unique to you.

Now, all of this is definitely going to have a role in understanding any given individuals autoimmunity. But unfortunately, you know, this is a new area.

We’ve got a lot, it’s actually a huge amount of information at the moment and it’s increasing, but there’s still a really a lack of strong, conclusive evidence. So I can’t say with any surety, what the definite associations are at this point in time. We’re still really early on in our understanding of the role of snips in general and also of course in autoimmune diseases, so a lot more information if needed in this area.

And if you don’t happen to have a full genetic screen for the intake paperwork, hopefully any functional medicine practitioner is going to be asking about your family history because this is going to tell us something regarding your genetic susceptibility for increased risk of developing autoimmune diseases.

I personally think that this is really important when we’re dealing with children, because we need to understand the risk of developing an autoimmune disease in a child.

Identifying Risk

If we can identify the risk early and we can identify a child that has the lifestyle variables involved. If there is a strong genetic predisposition, and also the child is exhibiting immune dysregulation and inflammatory symptoms early on. Then we have the opportunity to intervene before the auto immune disease really develops and we can have the potential then to change the trajectory of that process.

I think of course an ounce of prevention is better than a pound of cure, which is definitely true when it comes to autoimmunity. So, family history is the first place if you don’t have genetic screening, family history is the first place that we start to really understand where with auto immune disease is relevant to you.

And what we see is that autoimmunity tends to cluster in families. Presenting with lots of different autoimmune diseases sprinkled across the wider family knit.

So grandma might have rheumatoid arthritis and Uncle Sam has psoriasis and the Aunty Alma has Hashimoto’s and her sister has celiac disease. And you know, because they all have a different label, they all have a different diagnoses, perhaps nobody in the family has realized that each of these things are actually connected to each other and therefore that your child is at a higher risk of developing autoimmune disease as a result of that. So clustering and families is very, very interesting as there is this genetic susceptibility to autoimmune disease, but it’s not necessarily determining which disease develops in an individual.

There is a really high risk for first degree relatives of almost all of the autoimmune diseases. First degree relative of Crohn’s is up to 20 percent,  first degree relatives that multiple sclerosis is five percent and this increases up to about 40 percent for identical twins and so on.

So we know that many autoimmune diseases cluster, but it’s also interesting to note that some do not.

So for example, multiple sclerosis and rheumatoid arthritis don’t tend to appeal a in the same family. That’s not 100% of the time true, but it’s significantly less frequesnt than lets say Rheumatoid arthritis, Hashimotos or Celiac.

Auto immunity is complex. It’s multifactorial, it’s thought to present in those who have a certain susceptibility in their genetic chain, we call that the weak link in the chain.

But you must also have the environmental triggers in place.

So I no longer really think about it as the weak link in the chain because the reason that we have developed those attributes in our genes in the first place, your genes don’t ever make any changes unless they proffer some advantage of some kind.

So perhaps if you had genes that allowed you to have a massive response to an infection, you would be less likely to die of an acute infection. And that’s great, but it’s not longer the thing that everyone is dying from in the western world, so the benefit has now become a hinderance.

In this day and age where acute infection is not such a big problem, and chronic infection is much more prevalent. We see a change in the environment that those genes are in and we’re seeing this rise in autoimmune disease, which is potentially as a result.

The Environmental Trigger

So one way that people say that is that your genes load the gun and the environment pulls the trigger.

And another way of describing it is that except in the rare instance of single gene diseases, your genes never tell you who you are, our only what is possible and the rest is up to you.

And I think that that is extremely important to understand with autoimmune disease because if you think about it just as bad genes: I just have these bad genes and there’s nothing that I can do about that. Then you’re missing the point that there are so many variables in your environment that you have the ability to change.

And  when you understand that you can change a lot about your environment, the environment that your genes are in, then this has the potential to help you massively improve your quality of life, especially when you have already been diagnosed and you’re suffering with symptoms.

But also we can change the environment that your children are in and that your children’s genes are in as a way of preventing potentially preventing the development of autoimmune disease in the next generation. Then this interplay between genes and environment become possibly even more critical.

So that’s the end of genetics and autoimmunity. It’s a complex topic and I have tried to keep it simple and short. My next video will be on the gut andautoimmune immune disease, which of course is super important information and I’ve got some really, really mind blowing new information to share in that one.

So stay tuned. I hope you’ve enjoyed this video. Do leave me a comment if you found it useful, and thank you very much for watching.

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Robyn is a Clinical Nutritionist with a specialised interest in the Functional Medicine approach to health. Robyn is very involved with the field of Coeliac Disease, Gluten-Reactive Disorders and Autoimmune Disease. Her passion for the healing power of food, has led her to work with complex cases, involving multiple diagnoses, and chronic health issues such as ME, auto-immune diseases and fibromyalgia. She also has a passion for working with the growing tide of chronic, lifestyle mediated illness; diabetes, cardiovascular disease and obesity, and runs a lifestyle intervention clinic for these issues. Robyn works with patients to nutritionally support their bodies, so that they can heal. She has successfully helped many people around the world improve their health and increase their quality of life. Robyn sees clients in London, Tokyo and New York, and has a virtual practice that allows her to work with people all over the world.

Robyn Puglia

My mission in life is to share my knowledge in order to help people heal. I love to unravel the health stories and the biochemistry to get to the heart of the problem, and to help support nutritional and lifestyle changes that have the ability to transform people’s health. I have seen incredible changes in the health of my clients, and I hope to do the same for you.

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