Sweat Protein May Be Defender against Lyme Disease

Researchers from the Massachusetts Institute of Technology (MIT) and the University of Helsinki have discovered that a protein in human sweat may protect against Lyme disease. The findings could help patients whose symptoms linger months or years.

Their research was published in Nature Communications in an article titled, “SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.”

“Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown,” the researchers wrote. “Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant.”

They also found that about one-third of the population carries a genetic variant of this protein that is associated with Lyme disease in genome-wide association studies.

“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,” said Michal Caspi Tal, PhD, a principal research scientist in MIT’s department of biological engineering and one of the senior authors of the new study.

Lyme disease is most often caused by a bacterium called Borrelia burgdorferi. Most patients receive doxycycline, an antibiotic that usually clears up the infection. However, in some patients, symptoms such as fatigue, memory problems, sleep disruption, and body aches can persist for months or years.

Tal and Hanna M. Ollila, PhD, who were postdocs together at Stanford University, began this study a few years ago in hopes of finding genetic markers of susceptibility to Lyme disease. They decided to run a genome-wide association study (GWAS) on a Finnish dataset that contains genome sequences for 410,000 people, along with detailed information on their medical histories.

This analysis revealed three hits, including two found in immune molecules that had been previously linked with Lyme disease. However, their third hit was a complete surprise—a secretoglobin called SCGB1D2. The researchers discovered that this particular secretoglobin is produced primarily by cells in the sweat glands.

To find out how this protein might influence Lyme disease, the researchers created normal and mutated versions of SCGB1D2 and exposed them to Borrelia burgdorferi grown in the lab. They discovered that the normal version of the protein significantly inhibited the growth of Borrelia burgdorferi. However, when they exposed bacteria to the mutated version, twice as much protein was required to suppress bacterial growth.

The researchers then exposed bacteria to either the normal or mutated variant of SCGB1D2 and injected them into mice. Mice injected with the bacteria exposed to the mutant protein became infected with Lyme disease, but mice injected with bacteria exposed to the normal version of SCGB1D2 did not.

“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,” Tal said.

The researchers now plan to investigate whether applying the protein to the skin of mice, which do not naturally produce SCGB1D2, could prevent them from being infected by Borrelia burgdorferi. They also plan to explore the protein’s potential as a treatment for infections that don’t respond to antibiotics.