Systemic lupus erythematosus (SLE), commonly referred to as lupus , is an autoimmune disease where the immune system attacks the body itself. It is a difficult disease to diagnose and treat, for which there is no cure.
Which are the lupus signs?
Lupus is a very complex disease where we find varied symptoms that can also appear in other diseases. When the body attacks its own cells and tissues, it causes inflammation that can be confused with other autoimmune diseases. The most characteristic symptom, although not present in all cases, is a butterfly-shaped rash on the cheeks .
When the diagnosis is reached, the symptoms or outbreaks that appear in each patient can also be caused by different reasons. In some cases, it can be caused by an infection, sunlight, or taking certain medications .
Both factors make lupus a disease that greatly affects the quality of life of those who suffer from it, especially until it is diagnosed. Once done, patients face a new problem: there is no cure for lupus.
The only option that patients have is to control the symptoms and avoid possible complications or diseases that usually appear additionally. The treatments available for this disease are immunosuppressants, steroids, anticoagulants and other options that reduce or prevent inflammation.
A disease of unknown origin
One of the reasons why a cure has not been developed is because the cause of this disease has many unknowns , where the only thing that is known for sure is that it is caused by a malfunction of the immune system.
Many genetic mutations have been identified that are associated with lupus , and it is also known that some risk factors are sex (more frequent in women) and some genetic aspects, since sometimes a hereditary predisposition is found.
Numerous studies using genetic samples from patients and animal models have identified multiple genetic mutations associated with white blood cell function. Among all those mutations, one of them seemed to be important in mouse models: TLR7 .
The function of this gene in mice is to detect viral RNA and is also associated with the proper functioning of B cells, which are responsible for making antibodies . Some symptoms of lupus are related to antibodies that attack the body itself, so mutations in this gene would also fit in humans.
However, attempts to detect this mutation in patients have been in vain . Everything seemed to indicate that this mutation was not the origin of lupus in humans, although it seemed so in mice.
They find a mutation in the TLR7 gene in a teenager
A new study published last April in the prestigious journal Nature has described a patient suffering from lupus who has a mutation in the TLR7 gene , confirming previous studies in animal models.
Analysis of this mutation has allowed a group of researchers to replicate the mutation exactly in a mouse model . This model has revealed that not only is the mutation essential, but that the molecules that bind to this receptor, TLR7, are important in causing symptoms.
In this study they have shown that this mutation in TLR7 causes the B cells that generate antibodies to become “ autoreactive ”. The consequence is that the antibodies produced end up detecting their own elements, cells or tissues, and send signals for the immune system to attack.
Thus, autoreactive antibodies could cause a wide variety of symptoms , depending on which molecule our body targets. This characteristic could explain why the symptoms in patients are so different.
Finally, the researchers analyzed the blood cells of the teenager in whom they discovered this mutation. In doing so, they found some features that they had observed in the B cells of the mice, confirming the cause of the disease.
A first step on the right path
Mouse models showed that this mutation was sufficient to cause lupus in animals, although it cannot be ruled out that there are no additional mutations in humans that affect the development of the disease.
It is even possible that people who have a different mutation in this gene that by itself does not cause the disease, may be modulated by an infection caused by RNA viruses , as in the case of SARS-CoV-2 . In this circumstance, a genetic predisposition related to the TLR7 gene could trigger lupus.
Despite the fact that this discovery represents a clear advance in understanding the origin of this disease and proposes new therapeutic targets, as well as a diagnostic test, many questions remain unanswered.
References:
Brown et al. 2022. TLR7 gain-of-function genetic variation causes human lupus. Nature. doi: 10.1038/s41586-022-04642-z
