Michael T. Borchers, PhD, Associate Professor, Department of Internal Medicine, Division of Pulmonary Critical Care & Sleep Medicine, University of Cincinnati
Lymphangioleiomyomatosis (LAM) is a rare lung disease that occurs primarily in women and results in relentless decline in pulmonary function and ultimate respiratory failure. A multicenter randomized clinical trial called MILES, based at the University of Cincinnati and directed by Frank McCormack, MD, Chief, Division of Pulmonary, Critical Care, and Sleep Medicine, led to the approval of sirolimus therapy for LAM by the FDA in 2015. The MILES trial demonstrated that sirolimus stabilizes lung function and improves the quality of life in patients with moderate to severe LAM. It is not recommended that patients with mild disease begin treatment with sirolimus because the risks and benefits of therapy are not well studied in this group. Patient surveys have shown that understanding the optimal timing of commencement of therapy is important to those affected. Thus, it is important to develop clinically useful biomarkers that can help clinicians and patients predict individual disease trajectories.
Michael T. Borchers, PhD, an associate professor in the Department of Internal Medicine at the University of Cincinnati, and his team are investigating biomarkers that could predict disease progression in LAM patients. Thanks to the availability of patient samples and clinical data from a 5-year National Heart, Lung, and Blood Institute (NHLBI) LAM registry, Dr. Borchers’ group was able to identify proteins in the blood samples, and determine how the presence of these factors was related to changes in lung function over time. These candidate prognostic biomarkers, called UL-16 binding protein 2 (ULBP2) and ULBP3, are not normally found in healthy people. However, they can be found in hosts subjected to various stresses and pathological conditions. The simultaneous presence of both ULBP2 and ULBP3 in blood was associated with a greater decline in lung function over time than decline that occurred in patients with only one biomarker or no biomarker.
This discovery is important for two reasons. First, developing a blood test to predict loss of lung function will help LAM patients and doctors make better decisions about disease management. Secondly, it is known that these biomarkers interact with an immune cell type called natural killer cells. This discovery identifies a potential role for the immune system in the disease progression of LAM. Scientists will use this knowledge to better understand disease pathogenesis and to develop new, better therapies.Dr. Borchers’ work is an excellent example of the value of donor tissue in advancing the understanding and treatment of a rare disease such as LAM.