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Genetic Signature Discovery Could Improve TB Treatment

Gert van der Hoek

In Memoriam - Editor, Senior Moderator
Tuberculosis causes 1.7 million deaths annually, the number is growing every year.

Also a growing number of TB-patients with MDR-TB or XDR-TB (= drugresistant).

A real "superbug".

About one-third of the world's population has been exposed or infected with the TB bacteria,

but only 10% of these people with latent TB become ill with the active form of the disease.

This study seems to be an important step to develop a test to find out if you belong to the 10%.




Scientists Move Closer To Blood Test That Predicts TB Using Genetic Signature

Article Date: 19 Aug 2010

Some snips

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Scientists have moved a step closer to developing a blood test that one day will be able to predict which 10 per cent of people who carry the TB bacterium in a latent form will later go on to have the full blown disease: they have identified clusters of genes or a "transcriptional signature" in patients with latent TB that is also carried by people with the active disease.

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There are two forms of TB: latent and active. People with the latent form of the disease carry the bacterium but don't develop symptoms, in fact only 10 per cent of people with the latent form will go on to develop the active form. The active disease attacks mainly the lungs, but TB bacteria can also attack any part of the body such as the kidney, spine, and brain.

Unfortunately, our immune response to the bacterium is not straightforward and difficult to characterize. This is what has been holding back the development of new diagnostics, treatments and vaccines. It appears that susceptibility to the disease is not a matter of one or two genes, but clusters of genes, and maybe even relationships between those clusters, controlled by whether certain genes are switched on or off.

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So currently, while we can test whether people carry the TB bacterium, we can't tell which of the 1 in 10 carriers is likely to progress to active disease.

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They found that one particular blood-based signature, the "neutrophil-driven interferon (IFN)-inducible gene profile", was the strongest link between people with latent TB and those with active disease, and this "reverted back to that of healthy controls after treatment".

They also found that a subset of this signature discriminated active TB from other inflammatory and infectious diseases, and that while an "IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB".

They concluded that their study had found a hitherto unappreciated role for the type of signalling this signature controls in the development of TB and this could be important for developing new vaccines and treatments.
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"If you could predict which so-called carriers of TB will progress to the full-blown disease, this would have major ramifications for stopping the global epidemic."

"We just have to prove it now, but it's very promising,"


http://www.medicalnewstoday.com/articles/198254.php
 
Re: Scientists Move Closer To Blood Test That Predicts TB Using Genetic Signature

Re: Scientists Move Closer To Blood Test That Predicts TB Using Genetic Signature

In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection (BMC Infect Dis., abstract, edited)


[Source: BioMed Central, full text and abstract, links: <cite cite="http://www.biomedcentral.com/1471-2334/10/243/abstract">Abstract | In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection</cite>. Edited.]

In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection

Pantelis Constantoulakis, Eftihia Filiou, Nikoletta Rovina, George Chras, Aggeliki Hamgougia, Simona Karabela, Adamantia Sotiriou, Charis Roussos and Nikolaos Poulakis

BMC Infectious Diseases 2010, 10:243
doi:10.1186/1471-2334-10-243
Published: 18 August 2010


Abstract (provisional)

Background
Toll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of Mycobacterium tuberculosis infection. Tauhe purpose of this study was to investigate the in vivo expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.

Methods
Twenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells vs an endogenous house-keeping gene.

Results
The mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.

Conclusions
Our results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective up-regulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.

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Re: Scientists Move Closer To Blood Test That Predicts TB Using Genetic Signature

Re: Scientists Move Closer To Blood Test That Predicts TB Using Genetic Signature

Genetic Signature Discovery Could Improve TB Treatment

Posted on: Thursday, 19 August 2010, 10:25 CDT

Patients suffering from active tuberculosis (TB) have a specific pattern of genes in their blood, according to a new study from scientists which could lead to better diagnostic tests and improved treatment methods for those suffering from the often deadly infectious disease.

- snip -

The need for improved TB testing and treatment is great, suggests Reuters reporter Kate Kelland .

It is one of the oldest diseases still currently active and is among the ten leading causes of death on the planet, killing three people every minute. In spite of those statistics, "doctors say current diagnostic tests for TB have barely been improved in the last 125 years" and "current drugs for TB are at least four decades old," the Reuters reporter said in an article dated August 18.

Full article
 
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