New biomarker to identify lupus patients shows promise for treatment

A team of Montreal researchers has discovered a family of proteins partly responsible for the development of systemic lupus erythematosus (SLE). In addition to being a target for diagnosis, this biomarker opens the door to promising avenues for treatment. These results appeared in the journal Immunity.Previous studies have noted a significant increase in T follicular helper (Tfh) cells in the blood of SLE patients. These lymphocytes play a crucial role in the immune response, but the cause of this increase was not understood. Molecular immunology researchers from the Montreal Clinical Research Institute (IRCM) therefore compared Tfh blood cells from lupus patients with healthy individuals. They noticed a difference in the expression of the CBL and CBLB proteins, which are responsible for controlling cell multiplication: They were simultaneously downregulated.This link was confirmed in a mouse model when deletion of these two proteins led to an increase in Tfh lymphocytes, which then caused a lupus-like autoimmune disease. Mice that had only one of the two proteins removed retained relatively normal Tfh levels. The disease would therefore be caused by the simultaneous negative regulation of CBLs.This biomarker is common among affected patients, since it was found in 80% of them. This discovery could be a game-changer in the current diagnosis of SLE, which lacks precision and leads to cases of false positives. “We are trying to develop a diagnostic tool to detect these proteins from blood cells and analyze them for comparison with normal cells,” explained Dr. Hua Gu, co-author of the study and director of the research unit in molecular immunology from the IRCM.Ways to prevent the diseaseSince this deregulation is undetectable at the RNA level, the researchers put forward the hypothesis that the disease is not of genetic origin, but rather of an epigenetic or environmental order. Indeed, several environmental triggers of lupus have already been identified and include exposure to the sun, viral infections, stress or exposure to certain contaminants.These factors scramble extracellular signals in some individuals, leading to the downregulation of CBL cells. This phenomenon would then cause a cellular cascade that leads to the appearance of lupus. “Our biggest challenge is to identify the source of this downregulation to have a better understanding of the underlying mechanism,” noted Dr. Gu, who is also a professor at the University of Montreal’s department of microbiology, infectiology and immunology, and assistant professor at McGill University.The degree of regulation also seems to correlate with the severity of the disease. Thus, strong negative regulation is associated with a more severe form of the disease. For the moment, researchers do not know if this phenomenon is detectable before the appearance of symptoms. If so, early detection could help predict which patients are most at risk in order to take certain actions before illness occurs.By attacking healthy tissues in the body, lupus produces inflammation that causes swelling and pain in all organs. Current treatments target the symptoms and stabilize the disease without completely eradicating it. “Over time, lupus creates organ damage that is usually irreversible. If we can attack the molecule that is at the origin of this mechanism, we could cure the disease,” said Dr. Gu.

New biomarker to identify lupus patients shows promise for treatment

Register for free access or login.

Related Topics