Genetic mutation linked to lupus

A DNA mutation in a gene that senses viral RNA was identified as a cause of the autoimmune disease lupus, by an international team of researchers.

The study, published in Nature, was conducted by researchers at the Centre of Personalised Immunology at the Australian National University in Canberra, Australia. The study’s aim was to identify a biological cause of lupus. To accomplish this, scientists conducted whole genome sequencing on the DNA of a Spanish girl named Gabriella who was diagnosed with severe lupus at seven years old. According to researchers, an early and severe diagnosis of lupus is rare and indicates a single genetic cause.

During their analysis of the participant’s genome sequencing, researchers discovered a single point mutation in the TLR7 gene. Using referrals from the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, researchers found that other patients with severe lupus also had this mutated gene.

Researchers then conducted CRISPR gene-editing to introduce the mutation into mice and after, observed the mice’s health. The researchers found that the mice developed lupus-like symptoms, evidence that the TLR7 mutation causes lupus.

Although a small number of lupus patients have the mutation, many patients have signs of overactivity in the TLR7 pathway. These findings provide a foundation for future research and treatments for the disease.

“Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery,” said the study’s co-author, Carmen de Lucas Collantes, MD.