TSRI scientists demonstrate new technique to selectively suppress harmful immune responses

A team of researchers from The Scripps Research Institute recently demonstrated a new technique to improve the selective repression of unwanted immune reactions while keeping the immune system as a whole intact.

Hemophilia A is a disease that affects patients without enough of a critical blood clotting protein called Factor VIII and can lead to uncontrolled bleeding. Patients can take replacement Factor VIII as a biotherapeutic, but 20 to 30 percent of patients' immune systems attack the Factor VIII. TSRI's new technique selectively disabled immune cells responsible for Factor VIII rejection while leaving the rest of the immune system alone.

James Paulson, the chair of TSRI's Department of Cell and Molecular Biology, and his team found in a mouse study that by selectively initiating the destruction of white blood cells that recognize Factor VIII, the mice were more susceptible to treatment with therapeutic Factor VIII. The team used CD22, a specific type of sugar that binds to the receptor of a type of white blood cell called a B-cell. CD22 disabled the B-cells meant to detect Factor VIII without any negative side effects to the immune system.

"After we started, we realized the opportunity to exploit the receptor's natural function in ways that might be medically relevant," Paulson said.

While the human immune system is very efficient, it can initiate misdirected attacks that lead to allergies, autoimmune diseases and the rejection of therapeutic drugs and transplant organs. Paulson and his team want to extend the work to determine if the new technique is applicable to more complicated conditions like allergies and autoimmune diseases.

"We know that the issues are more complex," Paulson said. "But our technique, in combination with others, might work to address them."

The study was published on Monday in the Journal of Clinical Investigation.