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"Lupus is also called the disease of a thousand faces because no two cases are identical. There are several forms of lupus, the most severe of which, systemic lupus erythematosus, affects between 0.5 and 1 person in 1000. The prevalence of this disease is 9 times higher in women than in men," explains rheumatologist Paul R. Fortin, who teaches at the Faculty of Medicine of Université Laval and conducts his research at the ARThritis Research Center and the Research Center of the CHU de Québec - Université Laval.
Mitochondria are the power plants of our cells. From an evolutionary perspective, they are thought to be bacteria that were integrated into more complex organisms billions of years ago. When mitochondria exit cells, the immune system considers them foreign bodies and mounts a response against them. The antibodies that target mitochondria, their DNA, or their RNA are indicative of the trajectory a lupus case will take.
In people with systemic lupus, the immune system becomes hypervigilant and attacks one or more tissues or organs including the skin, muscles, joints, blood, blood vessels, lungs, heart, brain, and kidneys. There is still no cure for this disease.
"The available medications are used to calm the inflammatory storm that occurs during disease flares," continues the researcher. "Finding the right balance between alleviating symptoms and maintaining the immune system's ability to defend the body against infections is necessary."
At the time of diagnosis, healthcare teams do not know which organ is at risk of being affected or what the severity of the damage will be. "If we had that information, we could determine which treatment is most appropriate in each case," summarizes Paul R. Fortin.
Previous studies by his team suggested that certain antibodies targeting mitochondria - the cells' power plants - were more abundant in people with systemic lupus.
"Under stress or in disease states, mitochondria can exit cells and enter the bloodstream," explains the researcher. "The immune system then considers them foreign bodies because mitochondria have retained characteristics close to bacteria. It therefore produces antibodies to get rid of them."
To explore this lead, the research team used data from an international project, started in 1999, involving 33 centers across 11 countries. "We measured antibodies against mitochondria as well as antibodies against mitochondrial DNA and RNA in 1114 people, using blood samples collected from the time of diagnosis and up to 7 years later," explains Paul R. Fortin. "We continued to follow these patients afterward, which allowed us to see the trajectory of their disease over periods of up to 21 years."
The results of the analyses show that the three antibodies are more abundant in people with lupus than in healthy subjects. Furthermore, the level of each of these antibodies, both at the time of diagnosis and subsequently, can be associated with certain disease trajectories. For example, high levels of antibodies against mitochondrial RNA are associated with vascular problems in women, while high levels of antibodies against mitochondrial DNA are associated with kidney damage and mortality.
"Currently, there is no way to predict the evolution of a lupus case. Doctoral student Yann Becker, professor Éric Boilard and I have filed a patent application for a test using antibodies against mitochondria that could help us predict the disease's trajectory. If this test were to one day become accessible to healthcare teams, it would be a further step toward precision medicine, allowing for greater personalization of treatments offered to people with lupus."
The signatories of the study published in Annals of Rheumatic Diseases associated with Université Laval are Yann L.C. Becker, Éric Boilard, Emmanuelle Rollet-Labelle, Anne-Sophie Julien, Isabelle Allaeys, Joannie Leclerc, Tania Lévesque, and Paul R. Fortin.