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Surprise finding reveals how adaptive our immune systems can be

Date:
July 15, 2013
Source:
Garvan Institute of Medical Research
Summary:
Studies of patients with immunodeficiencies involving single gene mutations can reveal a great deal about our immune systems, especially when actual symptoms do not accord with clinical expectations. Australian scientists acknowledge such a gap between expectation and reality in a new study, which examines people with "Autosomal Dominant Hyper IgE Syndrome."

Studies of patients with immunodeficiencies involving single gene mutations can reveal a great deal about our immune systems, especially when actual symptoms do not accord with clinical expectations.

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."


Story Source:

The above story is based on materials provided by Garvan Institute of Medical Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Megan L. Ives, Cindy S. Ma, Umaimainthan Palendira, Anna Chan, Jacinta Bustamante, Stephanie Boisson-Dupuis, Peter D. Arkwright, Dan Engelhard, Diana Averbuch, Klaus Magdorf, Joachim Roesler, Jane Peake, Melanie Wong, Stephen Adelstein, Sharon Choo, Joanne M. Smart, Martyn A. French, David A. Fulcher, Matthew C. Cook, Capucine Picard, Anne Durandy, Miyuki Tsumura, Masao Kobayashi, Gulbu Uzel, Jean-Laurent Casanova, Stuart G. Tangye, Elissa K. Deenick. Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8 T-cell memory formation and function. Journal of Allergy and Clinical Immunology, 2013; DOI: 10.1016/j.jaci.2013.05.029

Cite This Page:

Garvan Institute of Medical Research. "Surprise finding reveals how adaptive our immune systems can be." ScienceDaily. ScienceDaily, 15 July 2013. <www.sciencedaily.com/releases/2013/07/130715091226.htm>.
Garvan Institute of Medical Research. (2013, July 15). Surprise finding reveals how adaptive our immune systems can be. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2013/07/130715091226.htm
Garvan Institute of Medical Research. "Surprise finding reveals how adaptive our immune systems can be." ScienceDaily. www.sciencedaily.com/releases/2013/07/130715091226.htm (accessed October 2, 2014).

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