August 17, 2020
In a new study published in the journal Immunity, Lupus Research Alliance-funded researcher Dr. Boris Reizis and his colleagues identified conditions under which immune cells called B cells begin to attack healthy genetic material (DNA). Dr. Reizis’ findings highlight the potential of drugs such as anifrolumab and BIIB-059 as potential treatments for lupus that may not only stop these attacks, but help prevent them from happening.
This work was made possible by the LRA’s highly prestigious Dr. William E. Paul Distinguished Innovator Award in Lupus and Autoimmunity which provides up-to-$1 million to allow each investigator to test promising approaches for potential new lupus treatments.
Dr. Reizis and his team found that when B cells are exposed to DNA and other molecules known as interferons, they reproduce. These “daughter” cells, known as plasmablasts, were created despite the mechanisms in the body that normally prevent immune cells from targeting DNA.
Plasmablasts (and B cells more generally) are immune cells that help defend the body against invading microbes like bacteria and viruses. These cells produce molecules called antibodies that stick to tiny pieces of the microbes. Other immune cells can then see the antibodies and release inflammatory molecules to kill the microbe. This process is normally tightly controlled, since B cells produce plasmablasts under the supervision of other immune cells whose job is to kill any B cells that might harm the body. However, during lupus something triggers B cells that may respond to DNA to produce plasmablasts and antibodies that target DNA.
To identify this trigger, Dr. Reizis and his colleagues created a mouse model of lupus with genetic mutations that led to the creation of DNA-targeting B cells like the ones that cause damage in human lupus patients. Previous research has shown similar mutations are found in human families in which lupus runs as an inherited disease. The researchers found that molecules known as interferons give directions to the DNA-targeting B cells to produce harmful plasmablasts and antibodies. Targeting interferons, therefore could be a good strategy to prevent this process.
Two drugs currently in development for treating lupus directly target the Type I interferon receptor (anifrolumab) and the cells that produce interferons (BIIB059), The findings in this study suggest that these therapies may quickly work to slow down the lupus disease process by reducing the number of plasmablasts and the amount of DNA-targeting antibodies.
