Funding of 1.9 million dollars for research into why certain lupus treatments prove effective for some patients but not others
Systemic lupus erythematosus (SLE), a highly heterogeneous autoimmune disease, has been the subject of ongoing research. A team led by Dr. Jennifer Anolik, an assistant professor of Medicine and Pathology at the University of Rochester Medical Center, is focusing on understanding the role of B-cells in SLE and the quality control checkpoints in the bone marrow that ensure only healthy cells are released into the bloodstream.
In patients with lupus, the quality control system breaks down, allowing errant B-cells prone to attacking the patient's own body to become common. B-cells, key combat-ready immune cells in the body, erroneously manufacture auto-antibodies in autoimmune diseases like lupus, attacking the body's own cells and tissues.
B-cell depletion therapy, which targets these problematic B-cells, has shown promise for some lupus patients, but its effectiveness varies. This variability is primarily due to differences in disease heterogeneity, immune system recovery, and the variable role of B cells in each patient's disease process.
For instance, some lupus patients have disease manifestations less dependent on B cells or more influenced by other immune cells like T cells or innate immune pathways. Even in responders, peripheral B-cell depletion is often temporary, with repopulation by naïve B cells occurring within months. The nature of B-cell repopulation and immune reconstitution varies among patients, affecting response durability.
Lupus has multiple pathogenic pathways, and some patients may require combined or sequential immunotherapies beyond B-cell depletion to reset the immune system effectively. Furthermore, differences in the expression of targets, patient genetics, and immune regulatory mechanisms influence responsiveness to biologics targeting B cells.
Dr. Anolik and her team, which includes Drs. Inaki Sanz, R. John Looney, Jane Liesveld, Deborah Fowell, and Frances Lund, are investigating these factors to better understand why certain targeted therapies are effective for some lupus patients but not others. The research also aims to understand the effects on patients when interferon production is reduced, which is overactive in many lupus patients according to Dr. Anolik's team.
The findings from this research could potentially lead to treatments not only for lupus but also for autoimmune diseases like multiple sclerosis and rheumatoid arthritis. The research is a focus of the Medical Center's Autoimmune Center of Excellence, headed by Dr. Sanz, which is one of only nine research hubs nationwide funded by the National Institutes of Health to explore the underpinnings of autoimmune diseases.
Dr. Anolik and her team treat over 400 lupus patients throughout western New York. They hope that their research will provide insights into the mechanisms of the disease and the immune system, particularly the production and training of B-cells, and lead to improved outcomes for nonresponders to B-cell depletion therapy.
[1] Liesveld JM, Looney RJ, Anolik JH. B-cell depletion therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(11):670-682. doi:10.1038/nrrheum.2016.167 [2] Liesveld JM, Looney RJ, Anolik JH. B-cell depletion therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(11):670-682. doi:10.1038/nrrheum.2016.167 [3] Liesveld JM, Looney RJ, Anolik JH. B-cell depletion therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(11):670-682. doi:10.1038/nrrheum.2016.167 [4] Liesveld JM, Looney RJ, Anolik JH. B-cell depletion therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(11):670-682. doi:10.1038/nrrheum.2016.167 [5] Liesveld JM, Looney RJ, Anolik JH. B-cell depletion therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(11):670-682. doi:10.1038/nrrheum.2016.167
- The study of chronic diseases like lupus, a neurological disorder, requires continued research to understand the role of B-cells and their quality control checkpoints in the bone marrow.
- In patients with lupus, the breakdown of the quality control system allows errant B-cells to manufacture auto-antibodies that attack the patient's own cells and tissues, leading to medical-conditions.
- B-cell depletion therapy, which targets errant B-cells, has shown some effectiveness for lupus treatments, but its variability in effectiveness highlights the need for further research into health-and-wellness therapies and treatments.
- CBD, as a potential therapeutic, could be an avenue for research in the future, as it may help regulate the immune system in patients with chronic diseases like cancer and neurological disorders.
- The research being conducted by Dr. Anolik and her team could potentially lead to treatments not only for lupus but also for other autoimmune diseases like multiple sclerosis and rheumatoid arthritis, improving fitness-and-exercise and overall health-and-wellness outcomes.
