Lupus: Defects in body's dead cell digestion system linked to autoimmune disease

A "window into the cause" of lupus may have been identified. Researchers have discovered defects in the body's cell disposal system leads to a lupus-like disease in mice – potentially paving the way for treatments to prevent or reduce the symptoms of the autoimmune disease in humans.

A team of scientists from St Jude Children's Research Hospital in Tennessee were building on previous research into the process through which dead cells are digested by the body. One process, LC3-associated phagocytosis (LAP), makes sure dead and dying cells are disposed of properly and researchers had been studying this in lab mice.

They noticed the lab mice with LAP defects were significantly smaller than those without the defect. While looking into the cause of this size difference, the team found the LAP-deficient mice had increased levels of inflammation, autoimmune antibodies and other changes to their immune system, such as kidney damaged. These symptoms are all associated with lupus in humans.

In their study, published in Nature, the team injected dying cells into the LAP-deficient mice. Findings showed they digested them less efficiently than mice without the defect. Repeated exposure to these dying cells sped up the signs of the lupus-like disease, including an increase in antibodies attacking healthy tissue.

Previously, studies have linked lupus to another system involved in clearing dead cells from the body – autophagy. In mice that had normal LAP, but had defects in autophagy, there were no problems in dead cell digestion, increased inflammation or the lupus-like disease.

Douglas Green, one of the corresponding authors on the study, said: "Defects in the clearance of dying cells have been implicated in the systemic lupus erythematosus [SLE - a type of lupus] disease process, and previous studies have suggested that the problem may stem from defects in autophagy. In this study, we showed that LAP contributes to SLE in mice and likely accounts for the previously reported genetic association between autophagy and lupus."

They said the findings suggest LAP is involved in the control of inflammatory diseases, and that there is a link between the clearance of dying cells, the processes involved and inflammation in lupus. Researchers now plan to look at LAP defects in humans with lupus, as well as investigate its role in other inflammatory diseases.

"We hope the findings offer a window into the cause of this devastating disease in some patients and an opportunity to improve treatment by developing novel approaches to prevent or reduce the inflammation and autoimmune response that characterise lupus," Green added.