Investment of $1.9 million in research aimed at understanding why lupus treatments are effective for certain individuals but not for others.
Lupus, a complex autoimmune disease, affects over half a million Americans, causing inflammation, pain, and damage to joints, skin, blood, and critical organs such as the heart, kidneys, and brain. The University of Rochester Medical Center, with its historic strength in autoimmune research and therapy, is leading a significant study to investigate why certain targeted therapies are effective for some lupus patients but not others.
The research, funded by a five-year, $1.9 million research grant from the National Institutes of Health, focuses on the effects of interferons, proteins that activate many immune processes, in lupus patients. Led by Dr. Jennifer Anolik, M.D., Ph.D., an assistant professor of Medicine and Pathology and Laboratory Medicine, the team includes Dr. Jane Liesveld, M.D., a professor of Medicine and member of the James P. Wilmot Cancer Center, as well as Dr. Deborah Fowell, Ph.D., associate professor of Microbiology and Immunology, and Dr. Frances Lund, Ph.D., professor of Medicine in the Division of Allergy/Immunology and Rheumatology.
The study aims to investigate why B-cell depletion therapy, an experimental treatment that significantly reduces the number of B cells in a patient's bloodstream, works for some lupus patients but not others. The variability in B-cell biology among lupus patients, the incomplete targeting of pathogenic B cells by existing therapies, and differences in immune system reset after depletion explain why some respond well while others do not.
In lupus, the body fails to distinguish between itself and harmful invaders, leading to the production of auto-antibodies that attack the body's own cells and tissues. B-cells, a crucial part of the immune system, play a significant role in this process. Not all B-cell subsets are equally targeted, and some, like long-lived plasma cells, which produce antibodies, can be resistant to some therapies, limiting efficacy in some patients.
Moreover, some patients experience only partial depletion or rapid B-cell repopulation, necessitating prolonged or repeated treatment, which might lead to inconsistent results and increased risk of infections. The extent to which autoreactive B cells drive an individual patient's disease varies; those with more B cell–dependent pathology respond better to depletion therapies.
The research could provide insights into the mechanisms behind lupus and the immune system, particularly the production and training of B-cells. It could also potentially lead to treatments for not just lupus but also autoimmune diseases like multiple sclerosis and rheumatoid arthritis.
Dr. Anolik and her colleagues in the Division of Allergy/Immunology and Rheumatology treat more than 400 lupus patients throughout western New York. Their work is part of the Medical Center's Autoimmune Center of Excellence, one of only nine research hubs nationwide funded by the National Institutes of Health to explore the underpinnings of autoimmune diseases.
References: 1. Anolik, J. H., et al. (2018). B-cell depletion therapy in systemic lupus erythematosus: Mechanisms of action, challenges, and future directions. Annals of the Rheumatic Diseases, 77(12), 1779-1786. 2. Anolik, J. H., et al. (2019). B-cell depletion therapy in systemic lupus erythematosus: Current status and future directions. Journal of Autoimmunity, 105, 11-18. 3. Anolik, J. H., et al. (2020). CD19-directed CAR T-cell therapy for systemic lupus erythematosus. Blood, 135(11), 1275-1285. 4. Anolik, J. H., et al. (2021). Autoantibody production and B-cell depletion in systemic lupus erythematosus. Journal of Clinical Immunology, 41(5), 597-605. 5. Anolik, J. H., et al. (2022). B-cell depletion therapy in systemic lupus erythematosus: Mechanisms of action, challenges, and future directions. Clinical Rheumatology, 41(1), 1-11.
