What are the causes and risk factors of lupus?

Key points to remember about the different forms of lupus.

Lupus is not caught like an infection. It is the result of an interaction between a susceptible genetic background and external triggers, which ultimately lead to a breakdown of immune tolerance.
Direct hereditary transmission of lupus is a myth. Lupus is not passed on directly to one’s offspring; rather, it is the result of a complex genetic combination involving more than 100 genes.
UV rays remain the main suspected trigger of lupus. However, tobacco use and exposure to silica in fact act as poisons for the immune system.
Oestrogens stimulate immune cells, which explains the higher frequency in women.
A unbalanced diet (excess refined salt, vitamin D deficiency) is an aggravating factor in inflammation.
Certain medications can trigger lupus, but once the offending drug is discontinued, the ensuing immune storm generally tends to subside.

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Lupus: how does it develop?

Contrary to popular belief, lupus is not an infectious disease. It is not caught through contact, blood, or air. In fact, understanding how it appears requires a change of perspective. Lupus develops when various factors, both internal and external, come together. It is often described as a two-step process: on the one hand, a biological predisposition, and on the other, a triggering factor. In other words, the body already has a certain vulnerability, and it is the environment that sets the disease in motion.

Lupus: a matter of biological predisposition.

Lupus is often described as being genetic, which can be a source of confusion. Lupus is not a hereditary disease in the strict sense. It is not automatically passed from parents to children. Nevertheless, there is indeed an underlying genetic background that favours its development. In this context, we speak of a hereditary predisposition to lupus .

A recent study has identified more than 180 genes that play a role in the regulation of the immune system. These genes notably influence the control of inflammation, the clearance of dead cells, and the production of antibodies. In some individuals, this genetic background makes the immune system more reactive, as if it were constantly on high alert.

It is not certain that the disease will manifest; however, the risk is higher.

≈ 66%

the heritability rate of lupus.

Lupus and its triggering factors.

The transition from a silent genetic background to an active disease depends on a decisive encounter with specific external factors. Like safety locks being forced open, these environmental elements break the body’s immune tolerance, unleashing an autoimmune reaction that had previously remained latent. Whether it involves the assault of UV radiation, a profound emotional shock, or a hormonal shift, these triggers act as the biological signal that sets everything in motion.

Oxidative stress: when the environment overwhelms the immune system.

Even in the presence of a biological predisposition, the disease does not manifest without external influence. It is at this point that the environment intervenes, triggering massive oxidative stress — a molecular onslaught that damages cells and forces the immune system to respond abnormally.

UV rays: Exposure to sunlight is among the main triggering factors. Acting like “molecular scissors”, UV rays break the chemical bonds of DNA, forcing skin cells to self-destruct by fragmenting their own genetic code. In a predisposed individual, this cellular “cleansing” process is defective. DNA residues accumulate and are then interpreted by the immune system as viral threats, triggering an abnormal inflammatory response.
Tobacco: Smoking plays a significant role in the worsening of lupus. In fact, tobacco smoke contains more than 7,000 chemical substances, including heavy metals and toxins that attack the body. Nicotine, which is also present in this smoke, speeds up the heart and raises blood pressure, while carbon monoxide (a silent gas) reduces the amount of oxygen in the blood, suffocating the organs.
This oxidative stress leads to the degradation of DNA, mistakenly activating inflammatory genes and driving the immune system to attack the body itself. This biological sabotage not only worsens symptoms, but also neutralises the effectiveness of essential treatments. Numerous studies indicate that it may increase the risk of developing lupus and exacerbate its progression.
A study conducted on 1,398 patients shows that lupus patients who smoke have a probability of therapeutic response that is twice as low as that of non-smokers. This interference suggests that the toxic components of cigarettes disrupt the action of the drug at the cellular level, making the disappearance of skin lesions much more difficult to achieve for patients exposed to tobacco.
Atmospheric pollutants: Environmental and occupational pollutants constitute an invisible danger. Whether inhaled—such as silica from industrial dusts and fine particles from exhaust fumes—or absorbed by the body, like heavy metals (lead, cadmium), these agents act as permanent “irritants”. Once in the bloodstream, they trigger massive oxidative stress that damages the DNA of cells. In predisposed individuals, this cellular degradation overwhelms the body’s detoxification capacity, forcing the immune system to attack its own tissues, thereby promoting the onset or worsening of lupus.

Lupus and the role of hormones.

The fact that nine out of ten patients with lupus are women is a striking feature. It highlights the central role of hormones. Oestrogens strongly stimulate the immune system, which can promote autoimmune reactions. This process then increases the expression of survival proteins such as BAFF, thereby supporting the unusual persistence of “rogue” B lymphocytes instead of eliminating them. They also enhance the production of interferon-α, the key orchestrator of lupus-related inflammation. At the same time, they reduce the activity of regulatory T lymphocytes. This prevents the body from naturally restoring balance in the face of excessive immune reactions, keeping the system in a state of constant alert. The most vulnerable periods are therefore those marked by hormonal disturbances, such as puberty or pregnancy.

80 to 90%

lupus patients are women.

In contrast, testosterone acts as a major immunological brake by inhibiting the production of pro-inflammatory cytokines, such as IL‑6 and TNF‑α. It also limits the maturation of B lymphocytes, thereby reducing the production of pathological autoantibodies, while enhancing the activity of regulatory T cells. This moderating role maintains a tolerant environment within the human body, thus preventing the immune system from launching a massive attack against its own tissues in response to harmless environmental signals. Studies have shown that some men with lupus sometimes have a low testosterone level, often dropping below 300 ng/dL, or an oestrogen level rising above 50 pg/mL, thereby exceeding the usual average range. This confirms that the balance between these two hormones is the true biological marker of this disease, far beyond one’s legal gender alone.

Psychological stress, a triggering factor in lupus.

Stress can act as a trigger for lupus, influencing two complementary aspects: hormonal and cellular. Several studies have highlighted the impact of stress as both a precipitating and aggravating factor in lupus. Psychological stress triggers the release of mediators such as cortisol, which lower the defences of immune regulators. A recent study shows that psychological stress and anxiety, as measured by clinical scales such as the GAD-7 (General Anxiety Disorder-7), are not only consequences of the disease but also drivers of cellular ageing. High levels of stress are correlated with premature shortening of telomeres, thereby indicating accelerated biological deterioration of the body in patients with lupus.

Lupus, a drug‑induced cause.

There is a specific form of lupus that is triggered by the use of certain medications. Several studies show that some treatments, such as isoniazid or certain biotherapies, alter the structure of proteins or DNA, which are then recognised by the immune system as foreign. Hydralazine is a striking example. It enters white blood cells, where it blocks DNA methylation and thereby mistakenly activates inflammatory genes, while also distorting structural proteins (histones). These alterations make the cell’s components unrecognisable to the immune system, which then identifies them as foreign and attacks them. This triggering effect is generally reversible. In most cases, stopping the treatment is enough to make the symptoms disappear and to restore biological order.

Diet, a potential inflammatory factor in lupus.

Nowadays, diet is no longer seen as a simple source of energy. Studies suggest that what we eat directly influences the immune system, almost like a chemical code transmitted to the body’s cells. With regard to lupus, although diet is not a direct causal factor, it can certainly affect how the disease progresses, either by reducing inflammation or by worsening it.

Excess refined salt: It has long been known that refined salt plays a role in hypertension. However, some studies have found that it also has an impact on the immune system. Overconsumption (around 10 to 12 g/day) activates an enzyme called SGK1, which acts as a genetic switch on T lymphocytes. This enzyme instructs these cells to transform massively into Th17 lymphocytes (inflammatory soldiers) instead of becoming regulatory cells that are supposed to calm the immune response. The former are known for their contribution to inflammatory reactions, acting through several pro-inflammatory cytokines, such as interleukins‑17, 21 and 22, which they secrete. For a person predisposed to lupus, this overconsumption can intensify the immune response and contribute to the onset or worsening of symptoms.
Alfalfa (lucerne): This is a rather unusual case, but it may be related to symptoms similar to lupus. Alfalfa sprouts and seeds contain a substance called L-canavanine, which can mistakenly be incorporated into the body’s proteins and alter their structure. These distorted proteins are then targeted as intruders by the immune system, triggering or worsening the inflammatory responses seen in lupus. One study suggests that people with lupus should completely avoid consuming alfalfa seeds and sprouts, as even small amounts may trigger disease flares.
Imbalance of the gut microbiota: The gut is often described as a second brain, but it is also a key pillar of our immune system. Studies show that an unbalanced diet, low in fibre and high in ultra-processed foods, can disrupt the intestinal flora, leading to a reduction in certain “beneficial” bacteria, particularly Faecalibacterium prausnitzii. This bacterium is very important because it produces anti-inflammatory substances and helps to maintain a healthy intestinal barrier. This imbalance, known as dysbiosis, weakens the intestinal barrier.
In certain cases, this allows some bacterial fragments to enter the bloodstream, putting the immune system into a state of constant alert. This phenomenon is now being studied as a factor that may contribute to the causes of lupus. One study highlights the central role of intestinal dysbiosis. An imbalance in the gut microbiota reduces the production of protective molecules (SCFAs) and makes the intestine “permeable”. The passage of bacterial debris into the blood triggers immune confusion through molecular mimicry, whereby the body ends up attacking its own tissues, believing it is fighting intestinal intruders.
Vitamin D deficiency: Vitamin D is not only beneficial for bones. It is also essential for modulating the immune system by preventing excessive reactions. It promotes calming cells (regulatory T lymphocytes) and restrains those that trigger inflammation. Patients with lupus, in particular, often present with vitamin D deficiency, generally defined by blood levels below 20 ng/mL, largely due to limited exposure to sunlight. This is why a daily intake is often recommended, most commonly between 800 and 2,000 IU depending on individual needs. However, some studies show that this deficiency may appear before the onset of the disease. Indeed, a low level of vitamin D in the body leads to a reduction in the performance of the cells responsible for managing inflammation. This allows more room for the processes linked to the causes of lupus.