Hidden TB Risk in Treating Autoimmune and Inflammatory Diseases

Scientists have identified how a protein used to treat autoimmune and inflammatory diseases can weaken the body's defense against tuberculosis (1^✔ ✔Trusted Source
Tuberculosis - World Health Organization (WHO)

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How a Deficiency in Tumor Necrosis Factor (TNF) Can Lead to Severe Tuberculosis

While TB is the leading cause of mortality from infectious disease in the world, the deaths represent just 5 percent of infections with Mycobacterium tuberculosis (Mtb). Mtb spreads through the air and usually infects the lungs. Researchers have long known that an acquired deficiency of "tumour necrosis factor" (TNF) can raise the risk of developing TB. Upending long-held assumptions about the immune system, the study, published in the journal Nature, revealed that a lack of TNF incapacitates a specific immune process in the lungs, leading to severe illness.

Jean-Laurent Casanova, from Rockefeller University in the US, said that TNF protects the lungs against TB. But otherwise, it plays “a limited role in inflammation and immunity. "The study focussed on recurring TB infections experienced by two people in Colombia -- a 28-year-old woman and her 32-year-old cousin. Both were repeatedly hospitalised with significant lung conditions. Both initially responded well to anti-TB antibiotics."

Yet even though their immune systems functioned normally they became sick again within a year. The team conducted a whole-exome sequencing on the two, as well as a genetic analysis of their respective parents and relatives to probe their recurring TB infections.

The two were found to be the only members of their extended family with a mutation in the TNF gene, which failed to function. As a result, the patient's alveolar macrophages, located in their lungs, were overrun with Mtb. The team noted that the lack of TNF in alveolar macrophages makes people susceptible to airborne TB (Mtb).

The discovery solves a long-standing mystery about why TNF inhibitors, which are used to treat autoimmune and inflammatory diseases, raise the chances of contracting TB. Without TNF, a key part of the defence against it is defunct, said the team.

Reference:

1. Tuberculosis - World Health Organization (WHO) - (https://www.who.int/news-room/fact-sheets/detail/tuberculosis)

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