Last updated Feb. 1, 2023, by Marisa Wexler, MS
 Fact-checked by Patricia Silva, PhD
Lupus is an autoimmune disease in which the immune system attacks the body’s healthy tissue; consequently, the disease can affect many organs and cause a wide range of symptoms. While it is not known exactly what causes lupus to develop, a number of potential factors have been identified.
What causes lupus?
The immune system is normally responsible for defending the body against invaders such as bacteria and viruses. For example, B-cells — a type of immune cell — can make specialized proteins, known as antibodies, that specifically bind to infectious targets and direct an inflammatory attack.
Under usual circumstances, the immune system will typically attack anything that is not recognized as part of the body, but it won’t attack the body’s own healthy tissue. This phenomenon is called “immune tolerance.”
In lupus, the immune system launches an attack against healthy tissue, in a breakdown of tolerance. As part of this autoimmune attack, B-cells produce antibodies that target the body’s tissues, known as autoantibodies.
A particular class of autoantibodies, called antinuclear autoantibodies or ANAs, is particularly common in lupus and found in nearly all cases of the disease. These antibodies specifically bind to targets in the nucleus, the cellular compartment where DNA is stored.
Lupus risk factors
It is not known exactly what causes the breakdown of immune tolerance that leads to the autoimmune attack characteristic of lupus. It is likely that many factors, including genetics, lifestyle, and environmental factors, all play a role.
Genetic factors and family history
Variations in several genes have been tied to an altered risk of developing lupus, with over 90 genetic loci (regions in chromosomes) having been identified. Many of these genes encode for proteins that are important for regulating immune function.
Because genetics can influence lupus risk, and genes are passed within families from parents to their biological children, people with a family history of lupus or other autoimmune diseases are generally at higher risk of developing the disease themselves.
For example, if a person’s first-degree relative (such as a parent or sibling) has lupus, that person has about a 20 times higher risk of developing lupus compared to the general population. If lupus affects one person in a set of identical twins — who share the same genetics — there is a 30% to 50% chance the other twin will develop the disease.
However, genetics alone is not believed to be enough to cause lupus, and the connection between genetic variants and lupus is currently not well enough understood to accurately predict a person’s risk based on genetics.
Race and ethnic background
Studies have reported that lupus is more common in certain ethnic groups. In particular, it is reportedly more common in Black populations and certain Indigenous tribes.
In the U.S., the prevalence of lupus is higher among Black communities compared to white communities. These discrepancies are thought to mainly be due to genetic variations that are more or less common in different ethnic groups, though other factors may also play a role.
Sex and hormones
Lupus is about nine times more common in women than men. This difference in risk is thought to be driven mainly by differences in levels of sex-related hormones, which can influence immune function.
In particular, high levels of estrogen (one of the main female sex hormones), which can trigger immune activity, has shown a link with an increased lupus risk.
The risk of lupus is highest during the so-called “childbearing” years — the time between menarche (a first menstrual period) and menopause when menstruation stops — because these are typically the years when estrogen levels are highest.
Smoking and air pollution
Cigarette smoking has been linked with an increased risk of a number of diseases, including lupus. Cigarette smoke can trigger inflammation in the lungs, which may help set the stage for autoimmune disease to develop or aggravate existing disease.
Exposure to air pollution and toxins such as silica and mercury — which can also trigger lung inflammation — have also been linked with a lupus risk, though more studies are needed.
Ultraviolet light
High exposure to sunlight and other forms of ultraviolet light may increase the risk of lupus or aggravate existing disease. People with lupus are known to be more prone to photosensitivity, or greater skin sensitivity to light.
It is thought that ultraviolet light can trigger inflammation in the skin, leading to a worsening of autoimmune disease in susceptible people.
Infections
A particular virus called Epstein-Barr virus, or EBV, has been strongly linked to lupus. EBV is best known as the cause of infectious mononucleosis (colloquially called “mono”), though it also can cause nonspecific flu-like infections, particularly during childhood. Most people are infected with EBV at some point in their life.
Studies have shown that a history of EBV infection is significantly more common among people with lupus than in the general population, which suggests that the infection may predispose towards developing lupus. However, more evidence is needed to establish a clear cause-and-effect relationship.
A few other viruses also have shown possible links to lupus risk, including parvovirus B19, human endogenous retroviruses, and cytomegalovirus.
Drug-induced lupus
Some medications can cause lupus-like autoimmune disease as an uncommon side effect. In drug-induced lupus, symptoms usually do not appear until after a few months or even years of continual treatment. Symptoms of medication-induced lupus usually disappear within months of the treatment being stopped.
Two medications with the highest risk of drug-induced lupus are procainamide, which is used to treat irregular heart rhythms, and hydralazine, which is used to treat high blood pressure. It is estimated that about 20% of patients on long-term therapy with procainamide will develop drug-induced lupus, whereas for hydralazine the rate is about 5%.
Other medicines known to cause drug-induced lupus include:
- isoniazid, which is used to treat tuberculosis.
- minocycline, an antibiotic used to treat bacterial infections.
- Tumor-necrosis factor (TNF) alpha inhibitors, a class of anti-inflammatory therapies that includes etanercept and infliximab.
- quinidine, used to treat irregular heart rhythms.
Lupus News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.