What are the causes and risk factors of lupus?

The 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.
The direct hereditary transmission of lupus is a myth. Lupus is not passed on to one’s offspring; it is rather the result of a complex genetic combination involving more than 100 genes.
UV rays remain the main suspected triggering factor for lupus. However, tobacco and silica exposure actually act as toxins for the immune system.
Estrogens stimulate immune cells, which explains the higher prevalence in women.
An unbalanced diet (excess refined salt, vitamin D deficiency) is an aggravating factor in inflammation.
Certain medications can trigger lupus, but once the drug is discontinued, the immune storm generally tends to subside.

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Lupus: how does it develop?

Contrary to common belief, lupus is not an infectious disease. It is not transmitted through contact, blood, or air. In reality, understanding how it appears requires a shift in perspective. Lupus develops when various factors, both internal and external, come together. It is often described as a two-step process: on 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.

People often talk about genetic lupus, 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, a favorable genetic background is indeed present. 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 regulating the immune system. These genes notably influence the control of inflammation, the removal of dead cells, and the production of antibodies. In some people, 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 predisposition to an active disease depends on a decisive encounter with specific external factors. Like safety locks being forced open, these environmental elements disrupt the body’s immune tolerance, unleashing an autoimmune reaction that had previously remained latent. Whether it involves the aggression of UV radiation, a profound emotional shock, or a hormonal shift, these triggers serve 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. This is where the environment comes into play by triggering massive oxidative stress, a molecular assault that damages cells and forces the immune system to respond in an abnormal way.

UV rays: Sun exposure is one of the main triggering factors. Acting like “molecular scissors,” UV rays break the chemical bonds in DNA, forcing skin cells to self-destruct by fragmenting their own genetic code. In someone who is predisposed, this cellular “cleanup” 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 worsening 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 increases blood pressure, while carbon monoxide (a silent gas) reduces the amount of oxygen in the blood, depriving organs of oxygen.
This oxidative stress leads to the degradation of DNA, mistakenly activating inflammation-related genes and driving the immune system to attack the body itself. This biological sabotage not only worsens symptoms but also neutralizes the effectiveness of essential treatments. Numerous studies indicate that it may increase the risk of developing lupus and worsen 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 drug’s action at the cellular level, making the resolution of skin lesions much more difficult to achieve in patients exposed to tobacco.
Air pollutants: Environmental and occupational pollutants are an invisible hazard. Whether inhaled—such as silica from industrial dust or fine particles from exhaust fumes—or absorbed into the body—such as heavy metals (lead, cadmium)—these agents act as permanent “irritants.” Once in the bloodstream, they trigger massive oxidative stress that damages cellular DNA. In predisposed individuals, this cellular damage overwhelms the body’s detoxification capacity, forcing the immune system to attack its own tissues, which promotes 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 point. It underscores the central role of hormones. Estrogens strongly stimulate the immune system, which can promote autoimmune reactions. This process then increases the expression of survival proteins such as BAFF, thereby favoring the unusual persistence of “rogue” B lymphocytes instead of eliminating them. Estrogens also enhance the production of interferon-α, the true orchestrator of lupus-related inflammation. At the same time, they reduce the activity of regulatory T cells. This prevents the body from naturally restoring balance in the face of excessive immune responses, keeping the system in a state of constant alert. The most sensitive 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, which reduces the production of pathological autoantibodies, while enhancing the activity of regulatory T cells. This moderating role maintains a tolerant environment within the human body, thereby preventing the immune system from launching a large-scale attack against its own tissues in response to harmless environmental signals. Studies have shown that some men with lupus sometimes present with low testosterone levels, often dropping below 300 ng/dL, or estrogen levels rising above 50 pg/mL, thus exceeding the usual average. This confirms that the balance between these two hormones is the true biological indicator of this disease, far beyond simple legal gender status.

Psychological stress, a triggering factor for lupus.

Stress can act as a trigger for lupus, influencing two complementary dimensions: hormonal and cellular. Several studies have highlighted the impact of stress as both a triggering and aggravating factor in lupus. Psychological stress initiates the release of signaling molecules such as cortisol, which weaken the vigilance of immune regulators. A recent study shows that psychological stress and anxiety, as measured by clinical scales such as the GAD-7 (Generalized Anxiety Disorder-7), are not only consequences of the disease but also drivers of cellular aging. High levels of stress are correlated with premature shortening of telomeres, indicating an accelerated biological deterioration of the bodies of patients with lupus.

Lupus, a medication-induced cause.

There is a specific form of lupus that is triggered by taking certain medications. Multiple studies show that some treatments, such as isoniazid or certain biotherapies, alter the structure of proteins or DNA, which are then recognized as foreign by the immune system. Hydralazine is a striking example. It enters white blood cells, where it blocks DNA methylation, mistakenly activating inflammatory genes while also distorting structural proteins (histones). These changes make the cell’s components unrecognizable to the immune system, which then identifies them as foreign and attacks them. This drug‑induced activity is generally reversible. In most cases, stopping the medication is enough to make the symptoms disappear and restore biological balance.

Diet, a potential inflammatory factor in lupus.

Nowadays, diet is no longer seen as just 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. In the case of lupus, although diet is not a direct causal factor, it can certainly affect the course of the disease, either by reducing inflammation or by worsening it.

Excess refined salt: It has long been known that refined salt plays a role in high blood pressure. However, some studies have found that it also affects 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 directs these cells to massively transform into Th17 lymphocytes (inflammatory “soldier” cells) instead of becoming regulatory cells that are supposed to calm the immune response. Th17 cells 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 reaction and contribute to the onset or worsening of symptoms.
Alfalfa (also called 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 reactions seen in lupus. One study suggests that people with lupus should completely avoid consuming alfalfa seeds and sprouts, because even small amounts may trigger disease flares.
Imbalance of the gut microbiota: The gut is often referred to as a second brain, but it is also a key pillar of our immune system. Studies show that an unbalanced diet, low in fiber and high in ultra-processed foods, can disrupt the intestinal flora, leading to a decrease in certain “beneficial” bacteria, particularly Faecalibacterium prausnitzii. This bacterium is very important because it produces anti-inflammatory substances and helps maintain a healthy intestinal barrier. This imbalance, known as dysbiosis, weakens the intestinal barrier.
In some cases, this allows certain bacterial fragments to pass into 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 of the gut microbiota reduces the production of protective molecules (SCFAs) and makes the intestine “leaky.” The passage of bacterial debris into the blood triggers immune confusion through molecular mimicry, in which the body ends up attacking its own tissues while 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 slows down those that trigger inflammation. Patients with lupus, in particular, often have vitamin D deficiencies, generally defined by blood levels below 20 ng/mL, largely due to limited sun exposure. 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 disease itself develops. Indeed, a low level of vitamin D in the body leads to reduced performance of the cells responsible for regulating inflammation. This leaves more room for processes involved in the causes of lupus.