Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Gene set predictor for post-treatment Lyme disease

We previously published about this research in a story titled “Researchers Identify Genes Linked to Long-Term Lyme Disease” which can be found here. The study was originally published in the scientific journal Cell Reports Medicine. You can read the full text of the study here. 

This research team was led by scientists at John Hopkins University and the Icahn School of Medicine at Mount Sinai.

What Happened?

Lyme disease is an infectious illness transmitted by the bite of a tick. When diagnosed and treated promptly, most patients can recover; however, current diagnostic methods are not always reliable. In addition, around 10-20 percent of patients develop post-treatment Lyme disease (PTLD), in which they continue to experience symptoms despite receiving standard treatment. The research team hoped to discover a distinct immune response in patients with long-term symptoms that could help improve diagnostic accuracy and further the understanding of post-treatment Lyme disease molecular mechanisms.

The scientists sought to find differences between patients with PTLD and the more typical acute Lyme disease. The study included a total of 152 people with long-term symptoms (all of whom were required to have received appropriate antibiotic treatment) and 72 people with acute disease. In addition, 44 healthy control subjects were involved in the study. The participants had a profile of their gene expression gathered using the mononuclear peripheral blood cells. The team used RNA sequencing for this process and machine learning in order to recognize the most relevant genes.

The team found that the PTLD patients had a gene expression that was distinct both from healthy controls and from patients with the acute disease course. In addition, they found 35 genes that were expressed differently in the Lyme disease patients when compared to the control group. The team concluded that if whole blood could be analyzed, these genetic differences could improve the accuracy of diagnosis. 

About Lyme Disease

Lyme disease is an infectious disease caused by bacteria of the genus Borrelia. This bacterium is commonly spread to humans through the bite of a tick. In the US, the species of tick associated with Lyme disease is called the deer tick or the black legged tick (Ixodes scapularis). A tick must be attached to a person for at least 36 hours to transmit the bacteria. Symptoms of this disease include a distinctive bullseye rash surrounding the bite, fatigue, malaise, headache, and fever. Delays in treatment can lead to more serious symptoms, such as facial paralysis, mood changes, memory loss, sleeping difficulties, meningitis, arthritis, and others. In most cases, prompt treatment can effectively cure the infection. Delayed treatment increases the chance of serious complications and long term, lingering symptoms. The number of cases of the disease appears to be growing annually. To learn more about Lyme disease, click here.

Why Does it Matter?

The biggest deficit in the management and treatment of Lyme disease is misdiagnosis or lack of diagnosis; current testing approaches and diagnosis based on signs and symptoms, such as the bullseye rash, have far from 100 percent reliability. As untreated Lyme disease progresses, symptoms worsen in severity and the risk of permanent or long-term complications greatly increases. With the number of cases of Lyme disease increasing annually, there is an urgent need to improve diagnosis so that more patients can receive timely interventions.

“There still remains a critical unmet need, as this disease so often goes undiagnosed or misdiagnosed.” – Avi Ma’ayan, Professor, Icahn Mount Sinai, Senior Author

The differences in gene expression that this study found could be a critical tool for getting more patients diagnosed and avoiding misdiagnosis. While improving diagnosis alone may not eliminate PTLD that develops in a certain percentage of patients, it could nevertheless help improve treatment outcomes.

“We should not underestimate the value of using omics technologies, including transcriptomics, to measure RNA levels to detect the presence of many complex diseases, like Lyme disease. A diagnostic for Lyme disease may not be a panacea but could represent meaningful progress toward a more reliable diagnosis and, as a result, potentially better management of this disease.” – Ma’ayan