Preclinical study identifies genetic misfire in lupus
Cedars-Sinai investigators have identified a "molecular switch" on a gene strongly associated with the autoimmune disease lupus, which appears to propel immune cells into overdrive, attacking and damaging healthy tissues and organs.
In the preclinical study published in the journal Science Advances, investigators looked at how the gene PTPN22 affects the way immune cells, or T cells, get activated in patients with lupus. In both human tissue and also a mouse model of lupus, investigators observed that a chemical change called phosphorylation acted like an "on" switch, sending immune cells into an overdrive state that causes autoimmune diseases, including systemic lupus erythematosus (SLE).
Approximately 26 million people in the U.S. have been diagnosed with an autoimmune disorder, according to the National Institutes of Health. Investigators believe the findings could point the way to new therapies for these patients.
"PTPN22 is one of the strongest known genetic risk factors for lupus. In our study, the chemical change we saw showed up more often in patients with lupus than in those without the disease," said Nunzio Bottini, MD, Ph.D., director of the Kao Autoimmunity Institute at Cedars-Sinai and senior author of the study. "When we blocked this 'molecular switch' in mice, the animals were protected from lupus-associated complications, like kidney disease."
Shen Yang, Ph.D., lead author of the study and research coordinator of the Technology Unit at the Kao Autoimmunity Institute, said that further research is needed.
"The results suggest it may be possible to target PTPN22 and reset the immune response to keep it from destructive hyperactivity in order to better control lupus and other autoimmune diseases," Yang said.
