In a serendipitous twist, scientists have found that a rare genetic disease more commonly affecting Ashkenazi Jews also protects them from tuberculosis.
Within the study, published within the journal PNAS, researchers found Gaucher’s disease (pronounced go-SHAY), a lysosomal disorder, offers unintentional protection against TB.
In line with an estimate, around 10.6 million people internationally became sick on account of tuberculosis (TB) and 1.6 million people died from the disease in 2021.
Nevertheless, 95% of people who find themselves infected with the TB bacteria don’t fall unwell. The immune system in these individuals manages to successfully kill the pathogen.
“My colleagues and I are excited about what makes some people vulnerable to TB, while others seem like protected. We use zebrafish to check the disease, as their immune systems share many similarities with those of humans, and it is feasible to govern their genes within the lab,” Lalita Ramakrishnan, Professor, Microbiology, University of Cambridge, and Laura Whitworth, Group Laboratory Manager, Department of Medicine, University of Cambridge, together said, ScienceAlert reported.
Gaucher disease is a rare genetic disease that affects Ashkenazi Jews disproportionately, with around one in 800 births. However the disease can affect anyone. The disease has relatively mild symptoms, including an enlarged spleen and liver, and anemia.
The enzymes present within the cells’ lysosomes break down unwanted material comparable to proteins and fats. Reduction in these enzymes can result in a build-up of toxic material.
This build-up could be very detrimental to the traditional functioning of cells called macrophages.
“One kind of cell that’s vulnerable to this build-up is the macrophage, a cell that ‘eats’ toxic material, including bacteria and waste products. In lysosomal disorders, the macrophages crawl and change into enlarged because they accumulate undigested material of their lysosomes, making them less in a position to fight infection,” the authors said.
When the researchers genetically engineered zebrafish modeled on Gaucher disease, they found the fish became “TB-resistant, fairly than susceptible.”
“The rationale for this resistance to infection was due to fatty chemical that accumulates within the macrophages in Gaucher disease. This fatty chemical was found to act as a solvent that may kill TB bacteria inside minutes by disrupting their cell partitions,” the researchers explained.
The Ashkenazi Jews went through centuries of persecution, living in ghettos and moving from country to country. Since TB spreads faster in poorer living conditions and densely populated areas, the Jews will need to have been highly exposed to TB.
“These fish unknowingly landed us in a debate that is been occurring in human genetics for a long time: are Ashkenazi Jews – who we all know are at a much greater risk of Gaucher disease – one way or the other less prone to get TB infection? The reply appears to be yes,” researchers concluded.