91制片厂

Nearly half a million people become infected with Lyme disease in the United States each year 鈥� a number expected to grow as climate change expands the range of the ticks that carry it. But despite its status as the country鈥檚 most common vector-borne disease, there is still no reliable way to detect the infection in its early stages 鈥� when treatment is most effective.

A team of researchers from 91制片厂 has proposed a way to detect the bacterial infection by looking for a unique indicator that occurs before the immune system is able to launch a specific response. The group鈥檚 method recently received a boost from a U.S. Department of Health and Human Services and the Steve & Alexandra Cohen Foundation initiative to finally find an effective test for the disease.

The challenge of detecting Lyme disease lies in the evasiveness of the Borrelia burgdorferi bacteria, which quickly moves into surrounding tissue once it enters the bloodstream, becoming virtually undetectable. Even the best tests are missing the early stages of infection about half the time, which means doctors are usually left to make a diagnosis based on symptoms and without confirmatory test results.

鈥淎ntibiotic treatment can prevent the disease from progressing to a late stage,鈥� said Mary Ann Comunale, EdD, an assistant professor of microbiology and immunology in Drexel鈥檚 College of Medicine who is leading the effort to develop a better Lyme diagnostic test. 鈥淏ut in many cases, the patient is not aware they have been bit by a tick or do not display the tell-tale bulls-eye rash. The symptoms of Lyme are nonspecific and the same as many other infections, so it can go undiagnosed beyond the window during which antibiotics would be most effective.鈥�

Comunale鈥檚 group has taken a unique approach to tracking the Lyme disease-causing bacteria, Borrelia burgdorferi, that looks closely at glycans. Glycans are carbohydrate modifications found on proteins that play an important role in immune responses.

During an immune response, these glycans can change, resulting in an altered function of proteins they decorate.  Depending on what that change is, the glycan can make the protein more or less efficient at clearing infections.

鈥淭ypically, during an immune response, glycans on immune proteins contain lower levels of galactose and sialic acid and an increased level of agalactosylated structures,鈥� Comunale said. 鈥淏asically, the glycans structures are smaller. This reduced size promotes immune activation by making it easier to bind with cellular receptors. But in Lyme infections, this is not the case. In acute stages of Lyme disease, the immune proteins actually increase their galactose and sialic acid content 鈥� which hinders the immune response and buys the disease more time to spread in the body.鈥�

This altered response, while deleterious to the immune system, is key to the team鈥檚 approach to early detection of Lyme disease.

鈥淏ecause the response is different from what is seen in other diseases that have clinical symptoms similar to Lyme, we can use the glycosylation pattern as a reliable biomarker,鈥� Comunale said. 鈥淚mportantly, we see these differences at an early time point when current tests would produce false negative results.鈥�

The method 鈥� which stands apart from most other diagnostic tests because it does not depend on the detection of Borrelia specific antibodies 鈥� was recently as one of 10 top performers in an HHS-backed competition, called the , to identify the most promising new approaches to testing for the disease.

鈥淧hase 1 received 52 solutions for detecting active Lyme disease infections in people,鈥� said a LymeX Diagnostics Prize statement. 鈥淪olutions incorporated techniques such as radiology imaging, genomics sequencing, and microfluidics; submissions also translated approaches used in diagnosing other infectious diseases, including COVID-19. Technical reviewers initially evaluated this highly competitive field, and then the competition judging panel assessed submissions according to official evaluation criteria.鈥�

Results from early phases of testing indicate that Drexel鈥檚 method could be more than 80% accurate at detecting a Lyme infection in its early stages, according to Comunale. And because it uses differences in glycans as its indicator, rather than the presence of antibodies, it can also be used to discern between a past infection and re-infection; and possibly provide a way to measure the effectiveness of treatment.

鈥淭he test specifically focuses on the Lyme bacteria鈥檚 dysregulation of the immune system before the body produces antibodies to the bacterial antigens, in a process known as seroconversion,鈥� Comunale said. 鈥淭his allows for earlier detection than other tests currently available. The test will also monitor response to a treatment and can distinguish between diseases with similar symptoms.鈥�

Comunale has been studying the behavior of glycans for decades. Her work initially focused on developing a way to use them as biomarkers to screen for liver cancer, which resulted in the invention of a noninvasive diagnostic that can identify hepatocellular carcinoma in its early stages.

鈥淭hese tumors only secrete a detectable protein biomarker in about 50% of cases, so their diagnostics suffered from the same low sensitivity in early stages of cancer,鈥� Comunale said. 鈥淟yme disease suffers from the same poor sensitivity during the early stages. Glycan changes are known to occur in cancers, autoimmune and inflammatory diseases. So we thought that a glycomic approach might be similarly successful in testing for Lyme.鈥�

The initial work was made possible by an award Comunale received from the Mary DeWitt Pettit MD Fellowship. With the boost from LymeX and support from the Coulter-Drexel Translational Research Partnership Program Comunale鈥檚 team, which includes Alison Carey, MD, and Joris Beld, PhD, and Benjamin Haslund-Gourley, researchers from Drexel鈥檚 College of Medicine; Kevin Owens, PhD, from Drexel鈥檚 College of Arts and Sciences; and Anand Mehta, PhD, from the University of South Carolina鈥檚 College of Medicine, will continue to develop and expand testing of the diagnostic.