I was speaking with a new client recently in an initial consultation. She struggles with lupus and a few other autoimmune diseases.
We got all the way through our appointment – we talked about her health history in depth, we analyzed her blood work and we worked on short and long term game plans for reversing all her main health issues.
At the very end I gave her the opportunity to ask any final questions.
“What causes lupus? I mean, why did this happen to me?”, she asked meekly.
This client was understandably feeling discouraged that this had happened to her and was disappointed that she was “born with the lupus gene” and therefore destined to this exhausting and painful life she was living.
I immediately wanted to make her feel better so I started telling her about the “autoimmune cascade” and how it wasn’t simply her genetics that contributed to the fact that she had lupus or any of her other health issues.
I explained that her genetics was only one piece of the puzzle and that there were two other factors that contributed to her situation as well.
I *think* I made her feel a bit better with this explanation – it certainly made her feel more positive about the prospect of rebuilding her own health.
I thought this information would be relevant to everyone who suffers from autoimmune diseases so I wanted to share a more detailed version of my explanation here.
In this blog post, I will discuss the 3 main causes of lupus and other autoimmune diseases that must be present for symptoms to occur.
I will also suggest a path for reversing this autoimmune cascade and reversing lupus, autoimmune diseases and eliminating symptoms.
Let’s dive in…
In 2012 Dr. Alessio Fasano presented a study that described a unique theory of how autoimmune diseases come about .
He suggested that, for someone to get an autoimmune disease such as lupus, three things must happen:
- There must be a genetic predisposition for lupus.
- There must be epigenetic triggers present.
- There must be intestinal permeability (aka “leaky gut”) present.
Who is affected by lupus, how they are affected and to what extent will be determined by these key points.
Let’s discuss each one of these a little deeper…
Genetics is the study of heredity and the traits people inherit from their family through their DNA.
Your genes that you inherit from your parents are set in stone, meaning there’s nothing you can do to alter them.
Generally speaking, the color of your hair, the color of your eyes, how tall you are and your foot size are all good examples of this.
Regarding inheriting a disease or condition like lupus, your genes are responsible for:
- disease susceptibility
- development of how the specific disease manifests itself (symptoms)
In other words, how likely you are to get lupus, as well as which characteristics of lupus you will develop, is predetermined in your genes.
The potential for a disease condition to show up in your genes does so through something called a genetic variant on an individual single nucleotide polymorphism or SNP (pronounced SNIP).
It has been shown that there are particular SNPs and genetic variants associated with different lupus symptoms.
For example, TREX1 (SNP) rs922075 (genetic variant) is common in people who have lupus associated neurologic disorders.
Here are a few more examples from some of the most common symptoms of lupus.
- ITGAM rs1143679
- FCGR2A rs1801274
- IL-6 174G/C
- VDR rs1168268
- HLADR2, HLADR3 rs2187668
- STAT4 rs7574865, rs11889341, rs7568275, rs7582694
- ITGAM rs1143683, rs1143679
- IRF5 rs2004640, rs2079197, rs10488631
- IRF7 rs4963128
- TNFS4 rs2205960
- DNAse I Q222R
- ITGAM rs1143679
- FGCR2A, FCGR3A
- VDR rs3890733
- Mirl146a rs2910164
These are just a few of the lupus symptoms with their respective genes and variants. If you would like to see a more complete list you can do so here.
Additionally, you can be either heterozygous (+/-, only one of your parents gave you this variant) or homozygous (+/+, both your parents gave you a copy of this variant) for a particular SNP and genetic variant.
A +/+ significantly increases the likelihood that you will manifest symptoms associated with the variant. It’s almost certain.
A +/- gives you more of a 50-50 chance of it.
But is that all there is to it?
It used to be thought that if someone had the genetic coding for a particular disease or condition that it meant they were guaranteed to get that disease.
We now know that this isn’t the case at all and that someone can have the genes and genetic variants for a particular condition and still actually never get it.
How can this be?
Let’s talk about that in the next section on epigenetics.
Epigenetics is the study of non-genetic influences on gene expression.
Meaning, how your genes express themselves for reasons other than your inherited genetic code.
As I eluded to in the previous section, you can have a genetic code for an autoimmune condition such as lupus hardwired into your DNA from your parents, but until that gene is “switched on”, so to speak, you may not actually have the disease at all.
In one study in was found that, in sets of identical twins with one twin having lupus, only 20% of twins both had it .
That’s why many of us don’t present with symptoms of lupus until we are adults. Perhaps the genes, and therefore the genetic susceptibility, have been their all along but until we get a non-genetic trigger to turn on the gene expression then we won’t have lupus.
Perhaps also that if we remove these non-genetic triggers that switched on our gene expression for lupus we could reverse the cascade and actually switch off our lupus genetics.
So, epigenetics are the “non-genetic” influences on gene expression. What does that mean?
Epigenetic triggers are those triggers from your environment.
Here are some of the most common environmental triggers that have been shown to turn on the expression of the lupus genes:
- cigarette smoke
- alcohol consumption
- chemical exposure
- UV light
- viral infections (i.e. EBV)
- sex hormone imbalance
- bacterial infections
- nutrient deficiencies
- food intolerances (i.e. gluten)
- stressful events
Perhaps you can think back and recall an event, an illness or even the birth of a child that coincided with the onset of your initial lupus symptoms?
Once one of these environmental triggers initiate a downward cascade it is thought there are three epigenetic mechanisms by which they can act upon.
These mechanisms include:
- DNA hypomethylation
- Histone modifications
- MiRNA profiling
The micro details of these three mechanisms is beyond the scope of this blog post.
However, it has been documented that immune cells (including B cells and T cells), cytokines and genes can all be affected epigenetically by environmental triggers via one of these epigenetic mechanisms which can bring about whatever symptoms of lupus you are genetically coded for .
It’s likely these environmental triggers that’s what causes lupus flare ups, lupus fog, lupus pain and the infamous lupus rash.
But that’s not all…
Leaky Gut (Intestinal Permeability)
In recent years there has been an increased focus of research on the gut as a potential site for inflammation to occur in those with autoimmune issues .
Here’s how a healthy gut should work:
- When we consume food it goes down into the stomach where it begins to be broken down into smaller components (i.e. protein is broken down into individual amino acids) via HCL and pepsin.
- It then passes into the small intestine where it is broken down further by digestive enzymes secreted from the pancreas.
- Once broken down into individual amino acids they should be assimilated through the epithelial cells of the small intestine into the blood stream for circulation and use by the cells of your body.
In people with leaky gut:
- Food particles generally aren’t broken down into their smallest components, rather they remain partially undigested in the small intestine.
- These food particles “leak” out between the tight junctions between the epithelial cells of the small intestine and trigger an immune response (activation of T cells and B cells).
- Since food is not being broken down into usable substrates and assimilated into the blood stream, you end up with various nutrient deficiencies in addition to the autoimmune response.
But what actually triggers a healthy gut to change to a leaky gut?
Why, it’s an epigenetic trigger, of course!
Zonulin is a physiological modulator of the tight junctions between the epithelial cells in the small intestine.
When there is an increase in zonulin released into the gut, the tight junctions, which are supposed to be closed “tightly”, open up and allow the passage of material from the inside of your gut (where it’s supposed to be) to the outside of your gut (where it’s not supposed to be).
These immune complexes that slip through the tight junctions trigger an immune response. As noted before, which way your body decides to present the autoimmunity is dependent upon your individual genetics.
Zonulin release is dependent upon several of the epigenetic factors we mentioned above.
Most notably, the triggers known to cause an increased release of zonulin in the small intestine include:
Meaning, people who have lupus and related autoimmune diseases can most often attribute their issues to either gluten consumption and/or a hidden bacterial infection in the gut (although they are not the only triggers, just the most common).
What Causes Lupus?
As you just learned, lupus and related autoimmune diseases occur at the intersection of genetics, epigenetics and leaky gut.
You need all three components present to create this “perfect storm” for autoimmunity.
- An environmental trigger, such as a bacterial infection, needs to be present.
- The bacterial infection causes an increase in zonlulin in the gut which opens the tight junctions and allows gut contents to “leak” out.
- A chronic immune response to these leaked gut particles leads to subsequent autoimmune symptoms based on your individual genetic susceptibility.
If this autoimmune cascade that results in lupus can flow in this particular direction and cause autoimmunity, can we reverse the cascade thereby reversing lupus and related autoimmune diseases?
A New Treatment for Lupus?
I often use the phrases “reversing lupus” and “reversing autoimmunity”.
We can accomplish both of these by reversing this progression to lupus.
Here’s the simple two step process of how we accomplish this:
- Heal your leaky gut.
- Remove the epigenetic triggers that are causing the leaky gut.
- Switch off your autoimmune genes.
This might mean healing the bacterial infection that you didn’t know you had, eradicating a parasite lurking in your gut, balancing your hormones and/or removing gluten from your diet – whatever your individual triggers are.
Now, I say “simple”, because the concept is simple – but it certainly isn’t easy.
It can take some time, patience and several functional medicine tests to figure out exactly what the root cause of your lupus is (I discuss how we do that here).
But it certainly CAN be done.
Depending upon how severe your case is and how well your triggers are hiding, it can be a 6 to 12 month process of finding and treating issues that are triggering lupus.
But you’ve already suffered for so long with your chronic fatigue, pain, insomnia and depression, isn’t it worth 6 months of your time and commitment to reverse the genetic – epigenetic – leaky gut autoimmune cascade and finally reverse your lupus?