LOS ANGELES (Oct. 10, 2025) —
Preclinical Study Links Lupus to Gene Misfire
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 which 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, PhD, 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, PhD, 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.
Other Cedars-Sinai authors include Shen Yang, Caroline Jefferies, Daniel Wallace, Eugenio Santelli, Yuan Zhan, Qinwei Chen, Michifumi Yamashita, and Richard Ainsworth
Other authors include Irene Choi, Myungja Ro and Jonathan Yoshihara
Funding: This work was partially supported by the grants from UCSD Graduate Training Program in Cellular and Molecular Pharmacology (T32 GM007752 to L.-A.M.R.) and National Institute of Allergy and Infectious Disease (R01AI151172 to C.A.J. and R01AI148073 to N.B.).
Antibiotics Reduce UTI-Related Delirium in Preclinical Study
Antibiotics could help prevent or reverse symptoms of delirium in patients with urinary tract infections (UTIs), according to a preclinical study in laboratory mice conducted by Cedars-Sinai investigators. Their findings, published in the journal Translational Psychiatry, could change treatment guidelines if validated through clinical studies in human patients.
Delirium is common among patients with urinary tract infection—and can also increase long-term dementia risk, said Shouri Lahiri, MD, director of Neuroscience Critical Care and Neurocritical Care Research, associate professor of Neurology at Cedars-Sinai, and senior author of the study.
Delirium refers to a sudden disturbance in brain functions including attention, awareness and cognition, usually caused by an underlying infection like UTI or pneumonia. Patients with delirium often ramble and are disoriented, have memory problems and may experience hallucinations or paranoia.
“Our goal was to address a key clinical controversy around whether or not antibiotics help when delirium is the only sign of a possible urinary tract infection,” Lahiri said. “Our findings challenge current guidelines that recommend against antibiotics for delirious patients without urinary symptoms and could change clinical practice.”
Investigators working with laboratory mice with urinary tract infections found that these mice developed hallmarks of delirium including inattention, memory problems and anxiety—and signs of brain injury and inflammation. Mice treated with antibiotics showed improved symptoms and reduced brain injury, with early treatment proving more effective than delayed treatment.
Additional Cedars-Sinai authors include Kevin D. Winzey, BS; Landon Scott, MSHS; Debbie Moreira, BS; Timothy S. Islam, BS; Catherine Bresee, MS; Jean Phillipe Vit, PhD; Warren G. Tourtellotte MD, PhD; Konrad H. Schlick, MD; Fayyaz S. Sutterwala, MD, PhD; and S. Ananth Karumanchi MD.
Funding: The work was supported by an F. Widjaja Foundation Research Grant (SL).
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