What Causes Lupus? (An up-to-date answer in 2023)

What causes lupus? That is a question with no known correct answer… yet!

Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease. Often debilitating and sometimes fatal… this condition presents from the immune system attacking your body’s own cells and tissue.

In essence, a lupus patient is being attacked by the same system that should protect them.

Life with lupus is unpredictable. With spells of illness (called flares or flare-ups) rotating between periods of inactivity (remission). You never know what’s around the corner. This is not only a pain for the patient, it creates a challenge for clinics.

– Click here to learn the many signs and symptoms that lupus patients can face –

The most frustrating fact is that there is no known cure or cause for systemic lupus.

So, it can feel like there is no way out – especially during flare-ups.

At times, the condition can also become a mental strain. Meaning not only does it feel like you’re always moving against the wind… but your head is stuck in a black cloud also.

You begin questioning, ‘Why me?’ and ‘What did I do to deserve this?’

Science suspects that people may well be genetically predisposed to lupus. But only go on to develop lupus when something in the environment triggers it. Through the likes of infections, certain drugs, or even natural sunlight. ^[1]

Hence, there are many factors that may play a role in this condition.

Here are 9 possible triggers of systemic lupus:

Genetics

The idea that genes contribute to lupus is nothing new.

The disease can run in families, and even more so in identical twins. Still, science cannot connect the family ties by simple ‘Mendelian genetics.’

This has led researchers to look high and low for potential causes. Even asking whether systemic lupus is the unexpected legacy of the Black Plague? 

– Click here to learn whether lupus is the unexpected legacy of the Black Plague –

Most lupus patients may have rare genetic variants in certain lupus-linked genes. These specific genes: “BLK” and “BANK1” can present alone or together. With either being common in those with systemic lupus. ^{[2][3][4][5][6]}

BLK and BANK1 both have negative effects on protein function. Leading to the suppression of both “IRF5” and “type-I IFN” in human B cell lines. This results in more malfunctioning “B cells”. Along with certain disease-causing white blood cells. This confuses the immune system. So, it can no longer tell the difference between invading bacteria, viruses, and your body’s own cells. ^[2]

What’s more, “IRF5” and “BLK”, alongside “STAT4”, not only have links with lupus. But, with rheumatoid arthritis and systemic sclerosis also. Meaning, susceptible genes may play a role in many autoimmune rheumatic diseases. ^[7][8]

Still, there are more than 80 genetic markers with common variations that science associates with systemic lupus. ^[9]

However, the biggest breakthrough came in 2022. Researchers made a discovery that points the finger towards a problem in a gene called ‘TLR7’. 

TLR7 is on the X chromosome, which could explain why lupus is more common in women. Women have two X chromosomes, while males only have one in usual conditions. Fingers crossed that this leads to better treatments in the future for lupus patients.

– Click here to learn more about this genetic discovery –

 

Nonetheless, having genes that ‘predispose lupus’ does not guarantee you will develop the disease. It does mean though that you will be more vulnerable to environmental triggers, such as

 

Internal Environmental Triggers

Hormones

While lupus is not a “woman’s disease”. There does appear to be an uneven number of women who have it. With ratios in research being as high as 20:1. ^[10] A stat that I hate as a man living with lupus.

This fact forces researchers to focus their attention on “oestrogen” … the female sex steroid.

Asking whether it might regulate the severity of lupus somehow. Or question if it could be a catalyst for developing the disease itself. Especially since lupus appears more in women of childbearing age. ^[11]

It is possible that many other factors could contribute to the sex bias of lupus. These include: ^[12]

• X-chromosomal abnormalities
• X-chromosomal inactivation
• Foetal micro-chimerism

Still, oestrogen does add to the severity and flares of systemic lupus. ^[13][14] The exact reason is unclear.

But oestrogen appears to trigger an immune response. One that accelerates the expression of lupus-linked DNA switches (“miRNA”). ^[15][16]

The hunger hormone “leptin” is one suspect. This is because it increases with both female steroids: ‘oestradiol’ and ‘progesterone’. ^[17] Having high levels of these can promote inflammation. Contributing to the development of an autoimmune condition. ^[18]

Glucocorticoid Receptors

One thing for certain is that this is a complex subject.

For instance, the immune and endocrine systems communicate with one another. So, disruptions in this communication could dictate how easily or severely you get lupus.

It could weaken the ability of your “glucocorticoids” to switch off inflammatory genes. From impairing “glucocorticoid receptors” – the primary receptors within immune cells. ^[19]

Some say that genetic changes in the glucocorticoid receptors may influence lupus development.

For example, there was a 32% increase in lupus risk in people who had a ‘C’ instead of a ‘T’ in one location. As well as those with an ‘A’ instead of a ‘C’ in another position. While two other genetic modifications may protect against lupus. ^[20]

Likewise, glucocorticoid receptors and oestrogen receptors also interact with one another.

Those with lupus seem to have lower levels of the oestrogen receptor “alpha proteins” in their resting T cells. In comparison to the T cells of your healthy friends. ^[21]

This could be a result of a more rapid turnover. Due to a defect in the protein-creating process of these two steroid receptors.

A shift that is likely to affect many pathways that influence T cell development. Which would explain the strong gender bias of systemic lupus. ^[21]

This may explain why some lupus patients react better to glucocorticoids, like prednisolone than others. ^[22]

Gut Microbiome

Our guts house trillions of micro-organisms known as the “micro-biota”.

This “microbiome” community plays a crucial role in our health. ^[23] For instance, it helps prepare the immune system during our early years. ^[24] Before continuing on to regulate the immune system throughout life. ^[25]

Ultra-processed foods, a stupid staple of the Western diet, will damage your microbiome.

It promotes inflammation and all forms of inflammatory disease. ^[26]

This could explain why African Americans top the lupus tables in the US. As does African-Caribbean ethnicity in the UK. Yet, Africa, as a whole, is rock bottom.

Science suggests children in Africa have a richer microbiome than European kids. Including more good bacteria that help digest plants.

And less of the nasty “Enterobacteriaceae” bad bacteria, which can cause issues like meningitis and pneumonia. All due to their natural, high-fibre diet. ^[27]

I don’t imagine you will see many fast-food joints in a Burkina Faso village.

Then there is always the “hygiene hypothesis”. Which states that disease can result from a lack of exposure to particular microorganisms. ^[28]

Old-friends theory

Graham Rock’s “old friends’ theory” argues that we have it wrong when it comes to necessary childhood infections. We’re talking, about influenza, chickenpox, and measles.

These are modern bugs – he believes. Rather, we are missing ancient microbes that cause hidden or mild chronic infections.

What we deem as threats today, the immune system views as ‘old friends’ that it needs to develop or function.

Think malaria and parasitic worms (“helminths”). Most of which are near-extinct in the Western world now. Thanks to public health measures and urbanisation. E.g., improved sanitation and control of food production. ^[29]

This idea is a hard thought.

However, a 2020 Japanese research paper supports this idea. It implies that intestinal tapeworms, “Hymenolepis microstoma”, might stop lupus in its tracks. Not only can they stop the production of antibodies, but they also prevent kidney damage. Even stopping lupus from developing in pre-disposed mice – when given early. Perhaps due to the induction of regulatory T cells. ^[30]

Gut Make-Up

Microbial makeup appears to be different in those with lupus.

A small 2019 study appears to be the most promising. Revealing that women with lupus had around five times more bacteria known as “Ruminococcus gnavus” in their guts. In contrast to women of similar profiles who did not have the disease and were healthy. ^[31]

Ruminoccocus gnavus is a family member of “Lachnospiraceae”. This family of spore-forming bacteria appears to be higher in lupus-prone mice. ^[32]

R. Gnavus itself has strong links to ‘Chron’s disease”. As well as allergies like asthma and rhinitis. ^[33]

They produce the potent inflammatory protein “TNFa”. But what’s more of a concern is that R. Gnavus feed off “mucin”. A key building block for the protective mucus lining of our guts. ^[34] Leading to what we know as “leaky gut”.

This supports the suspicion that bacteria leaking from the gut triggers the immune response seen in lupus. ^[31] Especially as intestinal microbial imbalances can lead to immune system effects throughout the body.

External Environmental Triggers

Bacterial Infections

Following on…

In reality, R. Gnavus is most likely one of many characters staring in the ‘enemy of the gut’.

When your gut community loses all order, microbiome ‘cities’ can begin to appear. These cities are what we call “bacterial biofilms”. They are like anarchist communities made from bad bacteria.

In short, they are bad news for your health.

Like a fortified city, they build these cities within a supporting wall called a “matrix”. One main material of which is the DNA excreted by the bad bacteria that it harbours.

Another building block is a protein deposit called an “amyloid”.

Evidence suggests that these curli/DNA complexes can trigger autoimmunity. Confusing the immune system to attack your organs and body. Through acting as danger signals, molecular mimickers, and microbial chaperones of nucleic acids. Resulting in a lupus-like disease. ^[35]

There are four bacterial families that contain ‘curli’ amyloids. Named so due to their curly, fibre-like appearance.

These include “E. coli”, and the food poisoning causing, “Salmonella Typhimurium”.

Both of which are a key focus in Lupus. For one, the complexes formed by the two can cause inflammation. As well as the self-attacking antibodies of lupus. This has been shown to be true in mice who are and are not genetically prone to lupus. ^[36]

Those not predisposed to lupus did have lower levels of autoantibodies than the others. ^[36]

Could this explain why some of us reach remission faster than others?

Other bacterial species can produce amyloids that can strengthen the biofilm.

These include “Staphylococcus aureus”. A bacterium that can set off an inflammatory response in mice that mirrors lupus. With all bells and whistles, including kidney disease and autoantibodies appearing. ^[37]

Science also suggests that long-term exposure to ‘staph’ may contribute to lupus in humans. ^[38]

Viral Infections

Over the years, researchers have held on to the idea that viruses could cause systemic lupus.

Epstein Barr Virus

None more so than the Epstein Barr Virus (EBV for short).

With no link to dirty Jeffrey. This virus is also known as the “kissing disease,” because it passes on through saliva. Unfitting I know. Due to this nature, most of us contract it as a teenager or young adult. For instance, when practising tonsil tennis.

In the UK, we refer to this virus as “glandular fever” or “mono” virus.

They should call it the virus with a thousand names!

Most people will resolve with lifelong immunity. It is rare for multiple cases or serious complications to appear.

Yet, it seems that its link with lupus is here to stay. A 2018 study found that half of the lupus-linked genes are home to “EBNA2.” [39]

When EBV infects a person, it produces this EBNA2 protein. This then recruits human proteins called “transcription factors” to bind to regions of both the EBV genome and our own. Together, they begin to change the expression of neighbouring viral genes.

“We were surprised to see that nearly half of the locations on the human genome known to contribute to lupus risk were also binding sites for EBNA2.” “These findings suggest that EBV infection in cells can actually drive the activation of these genes and contribute to an individual’s risk of developing the disease.”

– Dr. Harley (lead researcher) ^[39]

The researchers found that EBNA2 and its related transcription factors activate not only some of the human genes with links to lupus. But with several other autoimmune diseases, including: 

• Celiac disease
• Inflammatory bowel disease
• Juvenile idiopathic arthritis
• Multiple sclerosis
• Rheumatoid arthritis
• Type 1 diabetes

Viruses could work with other environmental triggers

EBV infection is not the only factor that contributes to the autoimmune conditions mentioned. Many of the regulatory genes that contribute to lupus – and other autoimmune disorders – did not interact with EBNA2.

Plus, some individuals with these activated regulatory genes do not develop the disease.

The study does shed light on how environmental factors can interact with the human genetic blueprint. Which, in the end, will have disease-influencing consequences. These include:

• Viral or bacterial infections
• Poor diet
• Pollution
• Other hazardous exposures

Could a virus change your DNA?

Your body produces “interferons” in the presence of viruses and other pathogens.

Their role is to alert nearby cells so they can heighten their anti-viral defences.

Hence, they are part of your immune system’s weaponry to combat danger. But, if interferon levels go too high, they can actually contribute to the development of autoimmune disease. As seen in both lupus nephritis and Sjogren’s syndrome. [40]

Virus-like DNA sequences can be inherent in your own genome… or the RNA transcripts they produce. This is what may then drive the production of interferons and contribute to disease.

Your DNA will have sequences taken from viruses that your ancestors got. Dating back many thousands of years ago.

These virus-like sequences can move around – causing genetic mutations. Playing a big role in the evolution of your genetic make-up.

An example is “Human Endogenous retroviruses” (HERVs), which could cover as much as 40% of your genome.

There are about 200 families of HERVs in total. Some of which have strong links to systemic lupus. These include HRES-1, ERV-3, HERV-E 4-1, HERV-K10, and HERV-K18.

Although dormant in most people. It is possible that environmental factors could set off these viruses. Triggering an autoimmune reaction.

Perhaps through “molecular mimicry”, which enables them to evade immune responses. Allowing it to induce defective “apoptosis”… programmed cell death. Which would result in “immune tolerance” and the production of “pathogenic antibodies”. [41][42]

Air Pollution

Science suggests that current smokers have a higher risk of developing systemic lupus. ^[43][44][45] Yet, researchers are not 100% sure why.

Cigarette smoking stimulates the expression of the “Fas receptor” (CD95) on B cells and “CD4” on T cells. This can induce autoimmunity ^[46] and boost the production of pro-inflammatory “cytokines.” ^[47] Throwing your cytokine balance out of sync – a state seen in lupus patients. ^[48]

But, cigarette’s link to lupus is more due to the toxic components within the smoke. They can induce “oxidative stress” and damage “endogenous proteins” and your DNA. This could lead to “genetic mutations” and “gene activation”. Both of which can play a role in systemic lupus. ^[49]

– Click here to learn more about oxidative stress and lupus – 

Most of the toxic components in cigarette smoke are more prevalent in the air around us. Many of which have strong ties to systemic lupus. These include:

• Tar
• Nicotine
• Carbon monoxide
• Polycyclic aromatic hydrocarbons ^[50]
• Free radicals ^[51]
• Heavy metals (e.g., arsenic, cadmium, lead and polonium) ^[52]
• Particulate matter ^[53]

They come from the likes of:

• Engine fuels
• Petroleum products
• Industry processes
• Agriculture chemicals

This makes them a real threat to those genetically predisposed to any autoimmune disease. Especially those who have to live or work in a polluted environment. ^[54]

Air pollution can also have a lasting effect on the young. More so, on the immune and cardiovascular systems. ^[55]

Thus, making air pollution a potential trigger for systemic lupus.

– Click here to Learn If Air Pollution is Affecting Your Lupus –

Vaccines

Some researchers do question whether vaccinations could set off systemic lupus.

To date, no vaccine has been shown to do so.

But, a few studies do show a possible link between lupus and some vaccines.

These are the vaccinations for: ^[56]

• Pneumococcal
• Tetanus
• Haemophilus influenzae type b
• Human papillomavirus (HPV)
• Hepatitis B
• Influenza/Flu

There are no two ways about it, vaccinations split opinion.

To some, they are the golden child of modern medicine.

To others, they are a chemical concoction. Carried over to the public to fatten the pockets of ‘big Pharma’.

No matter which side you support, there is one thing you cannot deny… the typical vaccine formula contains the components to trigger an autoimmune disorder.

Antigens / Molecular Mimicry

For instance, vaccines contain “antigens”.

Once in your body, these antigens may share proteins with your body’s own – what we call “self-antigens.” This can confuse your immune system into seeing these “self-antigens” as unfamiliar intruders.

The immune system doesn’t ask questions. Rather, it may well respond by attacking these cells with similar antigens. Damaging otherwise healthy joints, blood vessels, or other organs.

This is what science calls “molecular mimicry”. A potential player in autoimmune conditions like lupus. ^[57][58]

The Human Papillomavirus (HPV) is under the scope for doing this and sparking lupus.

Peptides are proteins in a shorter form. They play important roles throughout your body. What’s more, your body’s peptides share similarities to certain HPV peptides… and “natural killer cell receptors”. Both of which are dysregulated in systemic lupus.

These viral peptides are present in the three available HPV vaccines. Suggesting that cross-reactivity may follow both HPV infection as well as vaccination. ^[57]

Immune Adjuvants

Vaccines also contain substances to stimulate an immune response, so-called “immune adjuvants.”

Without adjuvants, many vaccines fail to provoke an acceptable immune reaction. Except for live-attenuated viruses. This suggests that the adjuvant may be the driving force behind the immune response of a vaccine. ^[59]

Aluminium Salts

The most common adjuvant in vaccines today is, “aluminium” salts.

This heavy metal can be toxic at low levels. So, there is a balance needed to achieve the necessary immune reaction. But with minimal side effects. Yet this can be difficult to pull off in practice.

What’s more, the same mechanisms behind this vaccine immune response can cause issues. This includes a variety of autoimmune and/or inflammatory problems.

When this happens, the diagnosis is, “Autoimmune/autoinflammatory Syndrome Induced by Adjuvants.” Or, “ASIA syndrome”. ^[60]

At least one research paper links aluminium adjuvants with lupus. ^[61]

Hydrocarbon Oils

Likewise, another adjuvant in commercial vaccines is the oil, “Squalene.” Science suggests this hydrocarbon oil can trigger the production of lupus-specific autoantibodies.

As can Incomplete Freund’s adjuvant.

This is a hydrocarbon oil that was an active ingredient in past vaccinations. ^[62]

Mercury

If you were born before 2003, mercury, or “thimerosal” were in most of your childhood vaccinations.

Even nowadays, it is still in tetanus and pertussis vaccinations, and certain flu vaccines.

This is a concern as mercury is the third most toxic metal to mankind. One that can cause: ^[63]

• Neurological conditions
• Metabolic and mitochondrial disorders
• Autoimmune diseases

Mercury poisoning also creates lupus-like symptoms in mice. ^[64]

Some say that you shouldn’t worry about thimerosal as it isn’t “methyl-mercury.” Rather it is “ethyl-mercury,” a close relative that behaves the same way. But, has a shorter half-life of around a third. ^[65]

Yet, ethyl-mercury could well be more invasive, more persistent in the brain, and more toxic than methylmercury. ^[66]

It just happens to get a lot less attention in the science circles.

“Perhaps the most important thing that I took away from the last meeting was that those of us who deal with vaccines have really very little applicable background with metals and toxicological research.”

– Dr. Martin Myers, director of the National Vaccine Program Office and host of the 2000 HHS-sponsored Workshop on Aluminium in Vaccines ^[65]

So, all-in-all vaccinations may increase the risk of developing systemic lupus.

However, there is a need for more research.

In particular, the effect that adjuvants can have on your body – and immune system. Regardless of whether you are sitting on the fence, or have chosen which side to sit on this subject.

This is more important today than ever before. It appears the pandemic has created a fascination for vaccinations now.

Drugs

Unlike vaccinations, the medical profession knows some medications cause lupus.

Named “drug-induced lupus.” This is the side effect of certain – unrelated – medications. In which symptoms overlap with those of systemic lupus. ^[67]

Unlike systemic lupus, this disorder is reversible – by discontinuing the specific capsule.

Yet symptoms can vary, with its onset being rapid or gradual. This can make diagnosing “drug-induced lupus” difficult.

Most patients with drug-induced lupus experience mild symptoms. These usually consist of: ^[68]

• Fever
• “Malaise” – the feeling of being unwell
• Weight loss
• “Polyarticular arthralgia” – pain in different joints throughout the body
• “Symmetric myalgias” – muscle weakness/tenderness

But these problems get worse the longer you’re on the specific medication. On the flip side, common issues for systemic lupus are rare for the drug-induced version. In particular: ^[68]

• Malar (face) or discoid (skin) rash
• Photosensitivity
• Oral ulcers
• Alopecia
• Renal (kidneys), or neurological (nerves) disorders

So, any of the above should signal that you have ‘true’ systemic lupus.

Which drugs cause Drug-Induced Lupus?

The list of medications that could cause lupus-like symptoms is still growing.

For instance, a further 42 drugs are under the spotlight now thanks to a 2019 study. Making the list 118 drugs long – at the time of writing. ^[69] Of these, the highest risk lies with: ^[68]

• Hydralazine (Apresoline)
• Procainamide (Pronestyl)
• Quinidine (Quinaglute)

The mechanism behind why these drugs cause lupus-like symptoms is a puzzle. Especially as the medications come from a variety of classes.

It is possible that some drugs could contain a functional reactive group that triggers autoimmunity. However, it is more probable that the medication goes through a metabolic transformation. Transforming into a reactive product. ^[68]

Diet and Lifestyle

It would be silly to ignore the role diet and lifestyle could play in causing lupus.

Gene Expression

As the saying goes, you are what you eat. The food you eat can turn genes on or off. This is what we call “gene expression.”

Eating a high-carb diet, over 40% of daily calories, puts your body in overload… resulting in inflammation. So, keeping your carbohydrates lower than 30%-40% can lower inflammation.

This is by way of turning off genes that have a role in immunological processes. ^[69] The same effect was seen with a restricted-caloric diet – a science-supported aid to lupus. ^[70][71]

DNA Methylation

Also, two drugs that cause drug-induced lupus may do so by altering DNA methylation. These are “procainamide” and “hydralazine.” ^[72]

Diet influences DNA methylation – as it needs the vitamins from the food you eat.

So, it’s not too surprising to see that a methyl-donor deficient diet led to lupus nephritis in mice. Whereas those fed diets rich in methyl group micronutrients did not. ^[73] This suggests that both poor diet and DNA methylation issues could play a role in lupus.

Plus, DNA methylation can pass on from parent to daughter cells. ^[74] A possible reason why lupus is much more prevalent in females.

Gut Dysbiosis

Likewise, we know both diet and lifestyle shape our microbiome the most. ^[75] For instance, exercise is a lifestyle choice that alters your gut makeup – for better and for worse. ^[76][77] Extreme exercise can damage the gut and impair its function. ^[78] As can life’s stresses and smoking. ^[79][80]

Together, these three factors could influence your risk of developing systemic lupus… or its severity. ^[81][82][83]

– Click here to learn 3 Things You Need to Know about Your Gut Bacteria and Lupus –

Final Thoughts

As this article underlines, ‘what causes lupus’ is a near-impossible question to answer. There is a reason why it is still unknown today.

It seems plausible that the cause is a disturbance in a person’s genetic build. Either through inheriting faulty genes or from damage due to an infection or pollution. Made worse by a poor diet and/or lifestyle over a long period of time.

It seems all possible causes of lupus have the power to mess up your gut bacteria and health. So, you can argue that the root cause starts in the gut. Either because of gut pathogens, or leaky gut… or both.

This may not help you find out the true cause of your disease. But it does highlight – in bold – the impact that your diet and lifestyle choices have on your risk or severity of lupus.

Keep in mind that the body is a system. Symptoms are a sign that there is a problem somewhere. My aim, and yours, should be to try and find out where and why. My best guess is the gut. What’s yours?

– Click here to learn the many signs and symptoms that lupus patients can face –

 

TAKE HOME NOTES:

A solution to this issue is to understand what science suggests may cause lupus. To check them against your own history and to comment or message, so we can gather information to hack the code that is lupus.

The goal of this website is to present all relevant research. As well as create a community for those with Lupus to discuss. All in aid of breaking the code, and figuring out how to beat Lupus!

There is One Power Treatment for Lupus that Your Doctor Doesn’t Discuss – but should!

Click here to Learn More.

I’d love to hear your thoughts on these factors. Especially which ones you believe play a bigger role in your systemic lupus. Please drop a comment or get in contact with me directly.