Scientists finally find a genetic cause of Lupus

Systemic Lupus is an autoimmune disorder that affects around 5 million people worldwide. With 50,000 people of which living in the UK. [1]

For those that are new to lupus, it is a chronic autoimmune disease that can:

  • Produce inflammation in organs and joints
  • Affect movement and the skin (butterfly rash)
  • Cause fatigue and sensitivity to light

In severe cases, symptoms can be debilitating and complications can be fatal. But what makes its worse is that there is no known cure or cause for the condition. But this could soon change thanks to a new study, which will be music to the ears of all lupus patients.

Keep reading to learn more.


Hope on the horizon for lupus patients

On 27th April of this year (2022), scientists from Australia analysed the entire DNA of a Spanish teenager named Gabriela Piqueras. [2]

Receiving her lupus diagnosis at the tender age of 7 years old, following a severe onset of symptoms, gave researchers a reason to believe that there was single genetic cause. Rousing them to research further.

In their genetic analysis, researchers found a single-point mutation in the TLR7 gene.

In their genetic analysis, researchers found a single-point mutation in the TLR7 gene of Piqueras’ genome. What’s more, they were able to further support this finding using referrals from Shanghai Renji Hospital.

To confirm that this mutation is a cause and not a consequence of lupus, the researchers used CRISPR to recreate the same mutation in mice. Lo and behold, these mice went on to develop the disease and show similar symptoms. Providing clear evidence that the TLR7 mutation was in fact the cause. Answering the question on every lupus patient’s lips, “What causes lupus?”


Researchers introduced the mutation into mice, which then went on to develop the disease and show similar symptoms.


How does the TLR7 mutation cause lupus?

“While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

– Professor Nan Shen, co-director of China Australia Centre of Personalised Immunology (CACPI)

The mutation the researchers identified causes the TLR7 protein to bind more easily to a nucleic acid component called ‘guanosine.’ Causing it to become more active.

This increases the sensitivity of the TLR7 immune cell, making it more likely to incorrectly identify healthy tissue as foreign or damaged. Triggering the immune system to mount an attack against it. Creating the main characteristic of autoimmune disorders and lupus.


Could TLR7 play a potential role in gender disparities of lupus if it’s the cause?

Fun fact, the TLR7 protein sits on the X-chromosome. [2][3] Could this explain why lupus is about 10-times more frequent in females than males?

The TLR7 gene sits on the X-chromosome, which is wrongfully coined the “female chromosome” by some. This is because, typically, females have two copies of the X-chromosome whereas males have only one. Perhaps explaining why lupus is much more common in women than men.

If you do not know, we all inherit an X-chromosome from our mothers. But our gender is determined by the chromosome that we receive from our father. If you’re a male, you got a Y-chromosome; being female means you were given an additional X-chromosome.

Usually, in females one of the X-chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

That said, this does not apply to all.

For instance, females can be born missing, or partially missing one of their X-chromosomes. This condition is known as ‘Turner Syndrome.’

Lupus is extremely rare in people with this syndrome, but there is at least one case. [4]

On the other end of the scale, females can be born with three X-chromosomes. ‘Tipple X-syndrome’ as it is named, increases a female’s chance of developing lupus by 3-to-4-fold. That is, a staggering 25-to-52 times higher than the risk to XY males. [5]

Likewise, boys and men can be born with an extra X-chromosome. This is called ‘Klinefelter’s Syndrome.’ Interestingly enough, males with this have a similar risk of developing lupus as females do. But 14-times higher chance than males with XY-chromosomes. [6]

Leaving no question that the number of X-chromosomes a person has will dictate their risk of developing lupus.


Does this study offer any new treatment options for lupus?


“I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully, the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

– Gabriela Piqueras (The Spanish subject of this study)


The researchers are now working with pharmaceutical companies to explore the development of, or the repurposing of existing treatments, which target the TLR7 gene. And they hope that targeting this gene could also help patients with related conditions.


This is exciting news.

Yet, it is not actually new news.


The TLR7 link to lupus goes back to 2006 when Dr Silvia Bollard made a major discovery regarding mice that develop lupus. She found that such mice have an extra copy of the TLR7 gene located on the Y-chromosome. [7]


Yes, that’s correct, an extra TLR7 gene of the Y-chromosome. But how?


The TLR7 gene lives on the distal end of the X-chromosome. This means it is situated away from the centre point, or point of attachment.

For example, your hand is ‘distal’ to your elbow.

Sometimes, for whatever reason, chromosomes can break up into fragmented pieces that then re-attach to different chromosomes. These are known as ‘translocations’, or ‘chromosome mutations.’ [8]

What Dr Bollard and colleagues found in their 2006 study was that this translocation of an X chromosome to a Y chromosome in lupus-prone mice creates a Y-linked autoimmune accelerator (Yaa) locus. Making their immune systems aggressive and further damaging their kidneys. [7]

Interestingly enough, similar results were also seen in a different research paper the same year. [9]

Still, Bollard’s study was extended and supported by two further research papers showing TLR7 to be the potential gene triggering lupus. [10][11]

Together, these studies give further clarity, which is good news as it highlights a true trigger of lupus that science can focus on. Let’s hope that researchers are working on new therapeutic drugs… and have been since 2010.

We can find comfort in knowing that there is at least a group in Japan that is working on an anti-TLR7 antibody. [12][13]

But it’s no easy task developing medicine to interfere with a gene without setting off some unwanted side effects.


Can you do anything to counter lupus now we know of this genetic mutation may be the cause of lupus?


There may be a couple of things you can do if you have lupus to help counteract the effects of this TLR7 mutation.


For one, you can ensure you take your Hydroxychloroquine tablet every day.


Anti-malaria medications like hydroxychloroquine, chloroquine, and quinacrine are TLR7 antagonists. That is, they are regulators that inhibit or reduce the TLR7 from flooding your body with pro-inflammatory signals. Creating what we call a ‘cytokine storm.’ [14]

Although their official job role is to prevent a person from catching malaria. They have been used since the 1950s to treat immune-mediated inflammatory disorders like rheumatoid arthritis, lupus and Sjogren’s syndrome. [15]

So, if hydroxychloroquine or alike is not in your medicine box, it may be worth asking your consultant the question.


The second step you can take is to increase your dietary fibre.


Research led by a Yale immunobiologist found that eating more fibre can help prevent the development of lupus in susceptible mice. [16]

The team of researchers first took notice of how a single bacterium, Lactobacillus reuteri, in the gut of the mice triggered an immune response leading to lupus. They then fed the mice ‘resistant starch’ – to mimic that of a high-fibre diet in humans. Finding that it prevented mice from developing the autoimmune disorder.

Resistant starch feeds and enriches good bacteria because it passes through the small intestine to reach the large intestine. This, in turn, causes the secretion of ‘short-chain fatty acids,’ which suppresses both the growth and movement of L. reuteri bacteria outside the gut. Preventing what would otherwise lead to the autoimmune disease.

The study also found an imbalance of gut microbes in a subset of lupus patients that was similar to what they observed in lupus-prone mice not given the starch diet. Showing that a high-fibre diet could be beneficial to prevent or better the condition for me and you.


– Click here to learn 5 unexpected ways dietary fibre benefits systemic lupus –




If you are one of the 5 million people on this planet who have lupus, there is no doubt you’ve been wondering what causes lupus.

Finally, there may be an answer to the question. All thanks to researchers in a 2022 study showing that a mutation in the TLR7 gene may be the cause. Seen in humans, most notably a young Spanish girl called Gabriela, but proven in mice. For once, there is hope for people with lupus.

The good people of science now need to work out how to inhibit this pesky TLR7 mutation without making your life any worse. A group of Japanese researchers are on it at least.

But until then, all you can do is ensure you take your hydroxychloroquine tablet each day and eat a natural diet full of fabulous fibre and nourishing nutrients.


Further reading:

1 Powerful Treatment for Lupus your Doctor doesn’t discuss – but should!

You will be Deficient in this Vitamin if you have Lupus: Here are 5 Reasons Why

Are Antioxidants good for lupus?


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