Two University of Alabama at Birmingham researchers have received Novel Research grants from the Lupus Research Alliance. The grants to Andre Ballesteros-Tato, Ph.D., and Frances Lund, Ph.D., are both aimed toward developing targeted therapies for lupus, a complex disease that has varied and widespread effects in the body.
Top: Andre Ballesteros-Tato, Ph.D.; Middle: Frances Lund, Ph.D.,; Bottom: John Mountz, M.D., Ph.D.In lupus, the immune system mistakenly produces self-damaging antibodies that attack the bodies of people with lupus, damaging their kidneys, brain, skin and other organs.
Ballesteros-Tato, an assistant professor of medicine in the Division of Clinical Immunology and Rheumatology, and Lund, professor and chair of the Department of Microbiology, are two of just nine researchers nationwide awarded these grants this year to explore lupus from many perspectives, testing new theories about what causes lupus. The grants are $100,000 a year for three years.
In lupus, specialized immune cells called T follicular helper cells act as a support system to aid and nurture the B cells that make the self-damaging autoantibodies. Ballesteros-Tato is seeking a way to selectively eliminate the T follicular helper cells without knocking out other types of T cells that are part of a healthy immune system. Such a targeted therapy would, in turn, power down the lupus-related B cells to block disease progression, without the risk of profound immune suppression.
Lund is focused on the B cells of the immune system that normally make antibodies to defend the body against infectious diseases but in lupus produce the self-damaging antibodies.
Specifically, she is investigating a subclass of rogue B cells that are found in some people with lupus, but not in healthy people. These cells, dubbed “T-bethi B cells,” have high levels of a gene-controlling protein called T-bet. Learning how these rogue B cells are different can reveal new targets for safer lupus treatment. This could improve existing therapies that remove all B cells from a person’s immune system, a step that lowers autoimmunity but leaves patients vulnerable to infections by bacteria or viruses.
These two Novel Research grants from the Lupus Research Alliance follow on the heels of a major award last year to John D. Mountz, M.D., Ph.D., to uncover root causes of lupus. Mountz, a professor of medicine in the UAB Division of Clinical Immunology and Rheumatology, was one of two recipients of the Dr. William E. Paul Distinguished Innovator Awards in Lupus and Autoimmunity. This award provides up to $1 million over four years to encourage exceptional investigators worldwide to pursue innovative research projects that pair unconventional creativity with sound science.
Mountz is investigating a new explanation for how lupus develops and why some people are at greater risk for flares and kidney disease. He has found that patients with high levels of the molecule interferon-beta in their early developing B cells are more likely to have higher levels of autoantibodies and kidney disease. Furthermore, African-Americans with lupus have higher levels of interferon-beta in these cells compared with Caucasians with lupus.
Mountz is investigating whether the high level of interferon-beta within those developing B cells causes them to grow into adult, autoantibody-producing B cells that trigger lupus. If so, this could lead to treatments to block interferon-beta for use in people with lupus, especially African-American patients, who have a higher risk of flares and kidney disease and are disproportionately affected by lupus.
At UAB, Lund holds the Charles H. McCauley Chair of Microbiology, and Mountz holds the J.W. and Virginia Goodwin and Warren D. Blackburn Jr. Research Chair in Rheumatology.