What can a TLR7 Gene Mutation Tell us About Lupus and Severe COVID-19 Infections?

May 12, 2022

A study published recently in Nature analyzed the whole-genome sequencing of a 7-year-old child diagnosed with severe lupus. Her genetics were of particular interest due to the fact that such a severe case of lupus with early-onset symptoms is considered rare and strongly indicates a single genetic cause. Their analysis revealed a single-point mutation in the TLR7 gene.

This finding was corroborated when the same gene mutation was also seen in other severe lupus cases from the US and the China Australia Centre of Personlised Immunology at Shanghai Renji Hospital. To further verify that it was this specific gene mutation causing lupus, the researchers utilized CRISPR gene-editing technology allowing them to introduce the gene mutation in mice. After the mice seemingly developed lupus themselves (by presenting similar symptoms), this provided significant evidence that the TLR7 gene mutation was the cause.

This gene mutation has been shown to cause TLR7 (Toll-Like Receptor 7 – a receptor on immune cells that acts as a sensor) to bind more easily and become more active. This increased activity essentially causes the immune cell to “overreact” and be more sensitive, leading to healthy tissues being incorrectly identified as pathogens/damaged tissue and the immune system unnecessarily attacking them.

Other research teams have also studied TLR7 mutations specifically regarding severe COVID-19 infections (1) (2), and they found that the mutation was actually causing TLR7 to become less active in that case. It is interesting to note that both an overactive TLR7 and a disabled TLR7 can cause immune cells to respond incorrectly and lead to autoimmune conditions. More study is needed to help illuminate the role TLR7 may play in other systemic autoimmune diseases, but it is clearly an area of importance.