Surprise finding reveals how adaptive our immune systems can be

Australian scientists acknowledge such a gap between expectation and reality in a new study, which examines people with 'Autosomal Dominant Hyper IgE Syndrome'.

Hyper IgE Syndrome arises from a mutation in the STAT3 gene. This makes patients slightly more susceptible than normal to blood cancers known as 'lymphomas', and exposes them to recurrent skin infections and pneumonia. While these symptoms are certainly a problem, laboratory experiments and animal models predict far more susceptibility to viruses and cancers than is actually the case.

PhD student Megan Ives, Dr Elissa Deenick and Associate Professor Stuart Tangye, from Sydney's Garvan Institute of Medical Research, discovered that the immune systems of people with Hyper IgE Syndrome have much more redundancy, or compensatory capacity, than expected. Specifically, the research team expected patients to be significantly less able to create effective 'killer T cells', the class of immune cells that destroy invading microbes and cancers. Their results are published in the Journal of Allergy and Clinical Immunology, now online.

"Under normal circumstances, the STAT3 molecule passes biochemical signals in T cells which instruct them to turn on their killing machinery. In Hyper IgE patients, who lack the gene, the signal just appears to take a diversion most of the time, and that seems to work," said Dr Elissa Deenick.

"There are certain molecules that Killer T cells need in order to become effective -- and possibly in the case of a very few viruses and lymphomas, Hyper IgE patients are unable to generate the signals necessary to make these molecules. However they do make effective responses against most viruses and cancers."

Associate Professor Stuart Tangye believes the study is important because it underlines the differences between results obtained through mouse model work and real human infectious diseases. "I believe it's just as useful to find an explanation for a prediction that didn't happen as it is to have a prediction confirmed," he said.

"Megan's work allows us to understand why Hyper IgE patients are not super unwell, as you would expect. That understanding is vital clinically, because it may allow us to address the actual symptoms more effectively."