Elissa Deenick and Stuart Tangye of the Garvan Medical Research Institute in Sydney, wrote a paper on research into the immune system of patients with an autosomal dominant syndrome (hyper-IgE syndrome). Article published online July 8 in the Journal of Allergy and Clinical Immunology.

Some cases of an autosomal dominant syndrome, also known as Job's syndrome, are due to a change in just one STAT3 gene.. The mutation affects several body systems, including the immune system, where it results in abnormally high levels of immunoglobulin E (IgE) protein in the blood, Pannochka, an online publication for girls and women aged 14 to 35, reports.. net People with hyper-IgE are slightly more susceptible to blood cancers (lymphomas), and they can also fall prey to recurrent infections such as skin infections and pneumonia, eczema, and sometimes bone and dental disorders. But while many of the symptoms of hyper-IgE can be quite severe, they are far fewer in number than previously thought based on animal studies..

These experiments indicated that the immune system of such patients should be more vulnerable to viruses and cancer than it turned out to be..

When scientists look at how changes in genes trigger disease, they are testing, in part, the effect of changes in genes on the biochemical signals that control cell behavior.. In the case of the STAT3 gene, the change affects signals from immune system cells called killer T cells that destroy invading microbes and cancer cells..

Testing the immune cells of patients with hyper-IgE syndrome, doctors expected to see the results obtained from tests on mice, namely, significant immune system impairment..

But to their surprise, they found that the immune systems of the Hyper-IgE patients turned out to be in better condition than expected: it seems that the lack of important signals for T cells was somehow compensated.. Could it be that there is some kind of fallback path through which some signals can be redirected

“Under normal conditions, the STAT3 molecule sends biochemical signals to T cells, which are programmed to “turn on the killing machine”. In Hyper-IgE patients who lack the gene, the signal takes a different route. There are certain molecules that need T cells in order to be effective - in the case of a very small number of viruses and lymphoma.

Patients with hyper-IgE are unable to generate signals that could reach these molecules.. Despite this, the molecules respond effectively to most viruses and cancer.”.

The researchers concluded that while STAT3 chains are required for many aspects of killer T cell activity, they may in some cases be compensated for by other signals and this explains the relatively mild susceptibility to viral disease in hyper-IgE patients..

Tanji points out that finding a refutation of previously predicted results is just as important as confirming them, especially if you understand the mechanism for achieving these results.. According to him, the findings show that it is not always worth taking on faith the results obtained in animals in relation to real human diseases..

This study helps us understand why people with autosomal dominant syndrome are not "

This is not the first study in patients with an autosomal dominant syndrome to show how mice can downplay signals in the human immune system.. In 2006, doctors in Japan showed how patients' cells showed severe disruption of cytokine chains, in stark contrast to earlier studies in mice..

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