Jefferson Investigates: Equity in Liver Transplantation; Immunity in the Eye; Inflammation in Multiple Sclerosis
New breakthroughs in understanding gender disparities in liver transplants, the eye’s defenses against disease, and inflammation-related nerve damage in MS.
Image Credit: © Adobe Stock Dmitriy Kandinskiy/265980850
Striving Towards Equity in Liver Transplantation
“Unfortunately, there are more patients in need of liver transplantation than there are available donors. This leads to long wait times and the risk of patients becoming too sick to receive a liver transplant,” says transplant hepatologist Danielle M. Tholey, MD. In fact, 15% to 20% of patients who are on waiting lists to receive liver transplants end up dying before being able to receive them. Disproportionately more white males receive liver transplants in the U.S., while women of all races often die waiting to receive a transplant.
In their recent study, Dr. Tholey and her team at Thomas Jefferson University wanted to identify why men seem to be receiving more liver transplants than women. They looked at race, sex, insurance and education of patients receiving liver transplants. They then grouped the patients by whether they received a liver transplant from a deceased donor or a living donor.
Studies have shown that patients who receive a liver from a living donor have a quicker recovery post-procedure and longer survival rates. The researchers found that liver transplants from deceased donors were more likely to be received by male patients, regardless of race. However, the sex disparities were attenuated in living donor liver transplantation (55% men vs. 45% women compared to 67% men vs. 33% women for deceased donation). Surprisingly, liver donations from living donors were most likely to be received by Black and Hispanic women than men, making the sex disparity less pronounced. Overall, women are disadvantaged in receiving transplants, but there are no definitive answers as to why this is, although it is an active area of study.
In addition, the study addressed liver donor demographics. Importantly and interestingly, live donors were more likely to be women than men.
“Patients are less familiar with living donor transplants so sadly, they make up a small number of transplants in the U.S., despite offering superior outcomes,” says Dr. Tholey, “Further, living donor transplants may help alleviate the sex disparities based on our data.” She adds that resources such as Donor Shield can help alleviate financial burdens that could deter patients from living donor transplants by providing financial support to assist with medical costs, missed work or legal support affiliated with being a living donor, so they simply can focus on helping to save someone’s life.
“Studies like these shine light on the persistent disparities in health care, and encouragement of living donor transplantation is one small step towards alleviating some of these disparities,” says Dr. Tholey.
By Moriah Cunningham
Image Credit: © Adobe Stock Ayesha/478200128
Researchers Discover New Role of Immune Cells in Eye Health
The eye is an immune-privileged tissue because of the need to keep blood vessels away from the central pathway of light and to restrict entry of inflammatory cells that could cause damage. This has prompted questions about how the eye manages inflammation when it occurs.
A new study led by Thomas Jefferson University researchers has revealed insights into how the eye handles inflammation, particularly in autoimmune uveitis, an inflammatory disease that bypasses the eye’s immune privilege and can damage healthy eye tissue.
Previous studies by Jefferson researcher Sue Menko, PhD, revealed that immune cells populate the surface of the lens in response to acute injury and prolonged inflammation in other regions of the eye. While this was the first demonstration of immune cells recruited to the lens surface, it also raised questions about their role in ongoing surveillance, and whether they may help resolve the inflammation.
Her team’s latest study, published in The American Journal of Pathology, answers these questions. The researchers found that macrophages with an immunoregulatory phenotype and Tregs are the immune cells actively recruited to the lens surface during inflammation. These immunoregulatory cells help restore balance and reduce inflammation. They also found that these immune cells remain on the lens surface until the inflammation is resolved.
“Debunking the thought that the eye could not care for itself is a big deal,” says Dr. Menko. “This helps us understand disease processes like uveitis and how they’re resolved in the eye. Maintaining a non-inflammatory condition in the eye is crucial to preserve vision, and we now know that the eye has inherent mechanisms to do that.”
MD-PhD student and first author Phuong Lee contributed to the study alongside researchers from the National Eye Institute and George Washington University.
The study highlights the importance of understanding the eye’s natural defenses, which could eventually lead to more effective treatment strategies for autoimmune uveitis. The next steps in Dr. Menko’s research focus on uncovering the mechanisms that recruit immune cells to the lens and identifying the earliest alert systems that trigger this immunoregulatory inflammation in uveitis and other inflammatory eye conditions.
By Queen Muse
Image Credit: © Adobe Stock SaroStock/774059193
Studying Inflammation in Multiple Sclerosis
Nearly three million people worldwide suffer from multiple sclerosis (MS). The disease is a result of an auto-immune response that involves immune cells attacking a patient’s own brain cells, leading to symptoms that include vision loss, decreased muscle strength and sensory issues. Relapsing-remitting MS (RRMS) is the most common form of MS, whereby patients have flare-ups followed by periods of remission. While there are multiple effective therapies to treat inflammation and prevent new flare-ups, a new study explores a potential way to halt on-going nerve damage.
Silva Markovic-Plese, MD, PhD and her team at Thomas Jefferson University have been studying RRMS for more than a decade. In a previous study, they noticed elevated levels of an immune chemical called, IL-11, in the cerebrospinal fluid surrounding the brain and spinal cord of RRMS patients. They wanted to explore why.
IL-11 is a cytokine that causes the blood cell growth. In the current study, researchers found that IL-11 also mediates migration of inflammatory cells to the brain – this contributes to disease progression of RRMS. They then hypothesized that blocking IL-11 could decrease symptoms associated with RRMS. They used an antibody to reduce the IL-11 levels in mice and found that this reduced disease severity. Specifically, treated mice had lower levels of multiple inflammatory markers and decreased disease progression compared to controls.
Although this study is still in the pre-clinical stages, Dr. Markovic-Plese says, “blocking IL-11 could possibly prevent disease development by blocking the early inflammatory response.” The therapeutic approaches Dr. Markovic-Plese’s lab tested are currently in phase I clinical trials for pulmonary fibrosis, a disease caused by autoimmune responses like those found in MS. If future studies on the neuroprotective effect of IL-11 antibodies continue to show promise, this treatment could be available for MS patients in the near future.
By Moriah Cunningham
