Gene combo causes susceptibility to tuberculosis

07 March 2010


This week it looks like researchers have discovered a key reason why some people are susceptible to TB (tuberculosis) and others aren't. Publishing in the journal Cell, Lalita Ramakrishnan and colleagues from the University of Washington think that it's the levels of an enzyme called LTA4H which give some people better immunity.

And it's not those with more of the enzyme who are the winners, nor people with the Mycobacterium Tuberculosislowest levels of LTA4H. Similar to Goldilocks and the three bears, it's actually those individuals who have a middling or 'just right' amount of the immune enzyme who have TB resistance.

People who are heterozygous or have two different versions of the gene which makes LTA4H have this middling amount of the enzyme. The researchers tested this in a controlled environment by looking at zebrafish which had been selected to produce different levels of the enzyme.  It soon became apparent that LTA4H was playing some role in their immunity. Ramakrishnan then compared her findings with human geneticists from Washington, Vietnam and Nepal to see if they were the same. And it emerged that it was this heterozygosity in people which produced the ideal levels of the enzyme.

What's interesting about this is that, for a long time it's been known that people with a nasty case of TB may improve if you give them a dose of anti-inflammatories. It may be that these people are producing too much of LTA4H and by giving them anti-inflammatories you reduce the effect of the enzyme to a medium level; this makes life difficult for the TB bacteria - making the patient feel better.

And it's an important finding because there are now many strains of TB which are drug-resistant. If you can tinker with the human immune system instead you might come up with a better solution to the problem. Plus there's the added bonus that LTA4H also confers immunity to other mycobacterial infections like leprosy.


Add a comment