Researchers have found how a protein produced by immune cells and used to treat autoimmune and inflammatory diseases raises the risk of tuberculosis (TB).
While TB is the leading
cause of mortality from infectious disease in the world, the deaths represent
just 5 per cent 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.
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