Lupus Study Links Abnormal RNA Splicing in Immune Cells to Potential Self-Attack

Researchers at the La Jolla Institute for Immunology and the University of Washington reported evidence that abnormal RNA processing in a type of immune cell may help explain why the immune system attacks the body's own tissues in systemic lupus erythematosus, or lupus. The findings were described in an October 28 announcement accompanying a study in Nature.

The scientists examined blood samples from 34 patients with lupus. According to the research team's account, 33 had neutrophils with unusual RNA-splicing patterns that were not seen in samples from healthy volunteers. RNA splicing is the process through which cells edit instructions before producing proteins. Errors can generate altered protein fragments, some of which may appear unfamiliar to other immune cells.

The team reported that these altered fragments, called neoantigens, could be recognized by T cells and B cells. Those cells ordinarily help protect against infections, but recognizing abnormal material produced by the body's own cells could contribute to inflammation. The research suggests a possible mechanism for the immune response rather than demonstrating that these changes initiate lupus.

The distinction matters because lupus is a complex autoimmune condition involving several interacting immune pathways. The researchers said it remains uncertain whether abnormal neutrophils are an underlying cause of the disease or a consequence of inflammation already underway. The small patient sample also means the observations require replication and further work across more diverse groups.

The study does not establish a diagnostic test, new medicine or cure. Its immediate contribution is evidence for a hypothesis in which altered protein fragments may become targets of an otherwise functioning immune response. Further experiments would be needed to determine whether interrupting that process can improve outcomes for patients.