Risk of developing TB down to specific genes, new Irish study finds

Researchers at Trinity College Dublin and St James's Hospital have discovered why some people are more at risk of getting tuberculosis [TB] than others. The findings, related to a persons genes, could lead to personalised treatments for those who develop this serious lung condition.

The work focuses on an important immune system gene called MAL. A number of studies at Trinity have shown that MAL is an important signalling gene, but not all people have the same version.

About 25 per cent of Europeans, including Irish people, have a different form of the gene; these individuals are more susceptible to developing tuberculosis.

Dr Clíona Ní Cheallaigh and Prof Ed Lavelle and colleagues at Trinity joined with St James’s professor in respiratory medicine and clinical researcher Prof Joe Keane to study the connections between MAL and the risk of developing the disease.

They discovered that tuberculosis risk was associated with MAL and its interaction with a second immune system gene called Interferon gamma.

If you have the more common form of MAL, it triggers a strong immune response from Interferon gamma but, if you have the other form, the immune response launched against tuberculosis is much weaker.

“Having this different form of MAL affects how intensely you respond to Interferon gamma – if you’ve one form you have a big response, if you have another form you have a dampened down response,” said Dr Ní Cheallaigh.

This means that those with the different form of MAL are more susceptible to infection with tuberculosis, the researchers write on Tuesday in the journal Immunity. Funding for the research came from the Health Research Board, the Royal City of Dublin Trust and Science Foundation Ireland.

Informed treatment

Knowing this means it becomes important to know what form of the gene a patient has. “It will inform treatment for conditions such as tuberculosis,” said Dr Ní Cheallaigh who is a clinician scientist funded by the Health Research Board and the HSE.

“We are talking about treating TB patients differently because of their genes,” said Prof Keane. “It is quite exciting because we found out how we can profile people and develop treatments targeted directly to them. This one is a paradigm shift.”

It also opens up the possibility of new treatments for diseases such as cancer and other infectious diseases given Interferon gamma is associated with these conditions as well, Prof Lavelle said.

Tuberculosis may sound like a disease from Ireland’s past but it can be a major killer. Globally, tuberculosis ranks alongside HIV as the leading cause of death worldwide, killing 1.5 million people during 2014.

The condition was kept under control for decades through the use of antibiotics, but overuse and improper use of these drugs have led to the emergence of multi-drug resistant tuberculosis, forms of the disease that resist antibiotic control.

An increasing number of drug resistant forms of tuberculosis are being discovered in Ireland. “We have a cure for TB but it takes six months, so we are looking for a better cure for TB.”