About half a million people become infected with Lyme disease each year in the United States — a number expected to increase as climate change expands the range of ticks that carry it. But despite its status as the country’s most common vector-borne disease, there is still no reliable way to detect infection in its early stages — when treatment is most effective.
A team of Drexel University researchers has proposed a way to detect bacterial infection by looking for a unique polymer-protein indicator that occurs before an immune response is triggered. The group’s method recently received a boost from an initiative by the US Department of Health and Human Services and the Steve and Alexandra Cohen Foundation to find an effective test for the disease.
The challenge of detecting Lyme disease lies in its obviousness. borrelia burgdorferi The bacteria, which after entering the bloodstream quickly migrates to surrounding tissues, become virtually undetectable. Even the best tests miss the early stages of infection about half the time, meaning doctors are usually left to make a diagnosis based on symptoms and without confirmatory test results. .
“Antibiotic treatment can stop the disease from progressing to a later stage,” said Mary Ann Comunale, EdD, a professor of microbiology and immunology at Drexel College of Medicine who is leading the effort to develop a better Lyme diagnostic test. . “But in many cases, the patient doesn’t know they’ve been bitten by a tick or doesn’t exhibit the tell-tale bull’s-eye rash. Lyme symptoms are non-specific and similar to many other infections, so it Out the window may be uncontrolled during which time antibiotics will be most effective.
Comunale’s group has taken a unique approach to tracking the bacteria that cause Lyme disease, borrelia burgdorferi, which gives a closer look at the glycan. Glycans are carbohydrate modifications found on proteins that play an important role in the immune response.
During an immune response, these glycans can change, resulting in an altered function of the proteins they decorate. Depending on that change, the glycan can make the protein more or less efficient at clearing the infection.
“Typically, during an immune response, the glycans on immune proteins have lower levels of galactose and sialic acids and an increased level of agalactosylated structures,” Comunale said. “Basically, glycan structures are smaller. This smaller size promotes immune activation by making it easier to bind with cellular receptors. But this does not happen in Lyme infection. In the acute stages of Lyme disease, immune proteins actually Growth Their galactose and sialic acid content – which hinder the immune response and give the disease more time to spread through the body.
This altered response, while detrimental to the immune system, is critical to the team’s approach to early detection of Lyme disease.
“Since the response is different from what is seen in other diseases with clinical symptoms similar to Lyme, we can use the glycosylation pattern as a reliable biomarker,” Comunale said. “Importantly, we see these differences at an early time point when current tests would produce false negative results.”
The method — which differs from most other diagnostic tests because it does not rely on the detection of Borrelia-specific antibodies — was recently placed as one of the 10 top performers in an HHS-backed competition called LymeX. called the Diagnostics Prize, to identify the most promising new ways to test for disease.
“Phase 1 received 52 solutions for the detection of active Lyme disease infection in humans,” the LymeX Diagnostics Prize statement said. “Solutions include technologies such as radiology imaging, genomics sequencing and microfluidics; The submission also translated the approaches used in the diagnosis of other infectious diseases, including COVID-19. Technical reviewers initially evaluate this highly competitive field, and then the competition judging panel assesses the submissions according to the official evaluation criteria.
Results from the early stages of the trial suggest that Drexel’s method may be more than 80% accurate at detecting 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 differentiate between previous infection and re-infection; and possibly provide a way to measure the effectiveness of treatment.
“The test specifically focuses on the deregulation of the immune system by Lyme bacteria before the body produces antibodies to the bacterial antigens, in a process known as seroconversion,” Comunale said. “This allows for earlier detection than other tests currently available. The test will also monitor response to a treatment and can differentiate between diseases with similar symptoms.”
Comunale has been studying the behavior of glycans for decades. His work initially focused on developing a way to use them as biomarkers to screen for liver cancer, which resulted in the invention of a non-invasive diagnostic that can identify hepatocellular carcinoma in its earliest stages.
“These tumors secrete only a detectable protein biomarker in about 50% of cases, so their diagnosis suffered from the same low sensitivity as in the early stages of cancer,” Komunale said. “Lyme disease suffers from the same poor sensitivity in early stages. Glycan changes are known to occur in cancer, autoimmune and inflammatory diseases. So we thought a glycemic approach might be equally successful in testing for Lyme.”
The initial work was made possible by an award Comunale received from the Mary DeWitt Pettit MD Fellowship. With a boost from LymeX and support from the team of the Coulter-Drexel Translational Research Partnership Program Comunale, which includes Alison Cary, MD, and Joris Beld, PhD, and Benjamin Haslund-Gourley, researchers at the Drexel College of Medicine; Kevin Owens, PhD, from Drexel College of Arts and Sciences; And Anand Mehta, PhD, of the University of South Carolina College of Medicine, will continue to develop and expand the diagnostic’s test.