Lupus Research Alliance Funds Projects Exploring Potential Therapies

The Lupus Research Alliance awarded Novel Research Grants to two University of Alabama at Birmingham (UAB) researchers who will use the funds to explore potential targeted treatments for lupus.

Besides UAB’s Andre Ballesteros-Tato, PhD, and Frances Lund, PhD, seven other researchers in the U.S. were awarded these grants to study new and existing therapies, as well as the root causes of lupus. The funds are for $100,000 a year for three years.

T follicular helper cells are a subset of T-cells that play a key role in immunity by helping B-cells in the production of antibodies against foreign pathogens. In lupus, this support is essential in the B-cell-mediated production of the damaging autoantibodies.

Ballesteros-Tato’s project, “Knocking out Destructive T Cells While Preserving Protectors,” will study approaches to eliminate T follicular helper cells without knocking out other immune cells, according to a UAB news story written by Jeff Hansen.

The strategy could potentially fine-tune B-cells to stop disease worsening without causing profound immune suppression.

Lund is focusing on a subtype of rogue B-cells called T-bethi B-cells, which are found in some lupus patients but not in healthy people. These cells have high levels of T-bet, a gene-controlling protein.

By evaluating what makes these rogue B-cells different, Lund’s project, “Zeroing in on Rogue B Cells,” could reveal new targets for safer lupus treatment. The strategy could improve current therapies that remove all B-cells from a person’s immune system, which lowers autoimmunity but increases susceptibility to infections.

The two grants follow the 2017 Dr. William E. Paul Distinguished Innovator Award in Lupus and Autoimmunity, which was awarded to UAB’s John D. Mountz, an MD and PhD, to uncover the underlying causes of lupus. This major award provides up to $1 million in funds over four years to support innovative research.

Mountz, co-director of the UAB Center for Aging, is exploring a new explanation for the development of lupus and why some people are at greater risk for flare-ups and kidney disease. His work was supported in 2017 by a one-year, $250,000 grant from the Lupus Research Alliance.

Mountz’s research revealed that patients with high levels of the molecule interferon-beta in early developing B-cells are more susceptible to higher levels of autoantibodies and kidney disease. The research also showed that African-American patients with lupus have elevated levels of interferon-beta in these cells compared to Caucasians with the disease.

He is using the funds to investigate whether the high level of interferon-beta causes the early B-cells to develop into adult, autoantibody-producing cells that cause lupus. If so, this pathway could generate treatments to block interferon-beta in lupus, especially in African-American patients, who are disproportionately affected by this condition.