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…
SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease
We previously published about this research in a story titled “This Protein from Sweat Could Offer Protection from Lyme Disease” which can be found here. The study was originally published in the research journal Nature Communications. You can read the full text of the study here.
This research was affiliated with the Massachusetts Institute of Technology (MIT) and the University of Helsinki.
What Happened?
Lyme disease is one of several infectious diseases that can be spread through the bite of a tick, a parasitic arachnid. Rates of Lyme disease and other tick-borne illnesses have been increasing, both in the US and worldwide. As the global climate warms, tick populations have been increasing, including among species that transmit this disease.
While in most cases Lyme disease can be treated effectively with a course of antibiotics, especially when diagnosed early, a certain portion of patients don’t fully respond to this treatment and suffer from long-term, chronic symptoms. This variability in response suggests that there may be factors that affect susceptibility to Lyme disease. However, these factors have received little study. The goal of this study was to evaluate possible factors, such as genetic markers, that could affect Lyme disease and treatment outcomes.
This research was a genome-wide association study (GWAS) that utilized data from FinnGen, a Finnish dataset, and Estonian Biobank. The set included the genomes of 410,000 individuals, 7,000 of which had been diagnosed with Lyme disease. The team found a total of three genetic variants that appeared to be more common in people that contracted the disease. Two of these involved immune molecules that prior research had associated with Lyme disease, but the third was a surprise discovery.
The third variant involved a secretoglobin called SCGB1D2. Secretoglobins are a group of proteins typically found in the lining of hollow organs, like the lungs. They contribute to the immune system response against infections. SCGB1D2 is primarily produced by the sweat glands. After identifying this protein, the researchers sought to understand how it could affect Lyme disease.
In the lab setting, the team exposed both normal SCGB1D2 and a version that they had mutated to the bacteria responsible for Lyme disease, called Borrelia burgdorferi. The normal type was effective at suppressing the bacteria’s growth, but the mutated version was only half as effective.
The exposed bacteria were then injected into mice. The bacteria that had been exposed to the mutated version caused Lyme disease in the mice, while the bacteria that had been exposed to the normal version did not. Similar results were then replicated by Estonian researchers using data from the Estonian Biobank.
The team isn’t certain why the mutated version was less effective, though the mutation did cause a shift in amino acids from proline to leucine. Overall, the researchers concluded that SCGB1D2 has a protective effect against the bacteria responsible for Lyme disease.
Why Does it Matter?
The result in the mouse study, in which the normal version of the protein prevented the mice exposed to the bacteria from developing Lyme disease, is an exciting development that could point to a different method of treatment:
“In the paper we show they stayed healthy until day 10, but we followed the mice for over a month, and they never got infected. This wasn’t a delay, this was a full stop. That was really exciting.” – Michal Caspi Tal, senior author, Principal Research Scientist, MIT, Department of Biological Engineering
Future research will continue to explore the use of the protein in mice, such as investigating whether SCGB1D2 applied to the skin could prevent Lyme disease (mice don’t produce the protein on their own). They also hope to study whether it could work in cases where antibiotics are ineffective.
“This protein may provide some protection from Lyme disease, and we think there are real implications here for a preventative and possibly a therapeutic based on this protein.” – Tal
About Lyme Disease
Lyme disease is an infectious disease caused by bacteria of the genus Borrelia. This bacteria 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.
