Allergy pioneer Professor Wayne Thomas
For many asthmatics, the microscopic house dust mites that thrive in warm, humid and dark environments are a big deal, producing allergens that can trigger their symptoms.
About 90 per cent of asthmatic children in Australia have an allergy to house dust mites.
The molecular studies of Professor Wayne Thomas, particularly on house dust mites, have provided critical knowledge for the development of new understandings of allergy and new diagnostics and therapeutics.
Professor Thomas joined The Kids Research Institute Australia at its inception in 1990 and led the Division of Molecular Biotechnology where he pioneered the use of recombinant allergens for investigation. These were patented for clinical application.
When he entered the field of allergens, several laboratories had started to define the substances that the mite made to cause allergy and determine the chemical structure. However progress was almost at a standstill because they could not be isolated in the quantities required for protein chemistry available at the time.
"My allergen discoveries and developments centred on a new approach that became available in the early 1980s," Professor Thomas said. "It was to isolate the genes that contained the genetic blueprint for proteins (their amino acid sequences) instead of purifying the proteins themselves in a process called molecular cloning.
"For this, the different genes of the mite were separated and propagated in different colonies of bacteria. This enabled two very important processes - namely the use of DNA sequencing to read the genetic code to identify the proteins encoded by the gene and to make the bacteria produce the protein from the gene in endless quantities (called recombinant proteins or allergens).
"The first house dust mite allergen that I examined in this manner was recognised to be an enzyme that the mite used to digest its dinner. The second was a protein of then unknown function but now known to be critical for immunity to infection."
They were the first major allergens from any common source to be identified and soon became a subject of undergraduate textbooks.
The central focus of Professor Thomas' continuing work was to use the molecular approach to define other potential house mite allergens and to measure their contribution to overall allergy response. This found that more than half of allergy of all subjects sensitised by the house dust mite allergens were directed by the first two allergens and that most of the rest were linked to only five other proteins.
Professor Thomas said this molecular identification of allergens and the use of recombinant allergens for diagnosis over the past two decades had been one of the most easily identifiable recent advances in the allergy field.
Recombinant DNA technology provides the means for producing molecules that mimic the properties of the natural allergens and can be used to diagnose and develop desensitisation therapy for allergic people. It has enabled many investigations to help understand how the allergy develops and how it causes disease.
Laboratories elsewhere in the world have used many of these same strategies to move forward with the cloning of pollen, cat, cockroach, fungal and other allergens.
An important discovery made by Professor Thomas with Associate Professor Belinda Hales, the head of the Allergy and Infectious Disease Research Group, was that children with persistent and recurrent asthma, requiring hospitalisation, had allergic responses restricted to the same allergen components as children with mild allergies.
"Our discovery that children with persistent and recurrent asthma lacked the production of protective IgG antibodies rather than producing more of the disease-causing IgE antibodies or responding to more allergens stands out as example of a finding that required the use of pure and recombinant allergens," he said.
Professor Thomas said the commercial potential of the allergen cloning and the need to link with pharmaceutical companies was recognised early.
"New diagnostic microchip technologies that allow all common allergies to be simultaneously tested with a single test of a small blood sample require the pure allergens that we produced and their use will further increase when health care funding and insurance arrangements are settled," he said.
He also said that the therapies in the pipeline that use the knowledge and patents of the cloned allergens are shaping up to make new-generation immunotherapy a reality.
"The efficacy trial of the UK company Circassia Ltd, in particular, showed a short four-injection treatment protocol with allergen components produced rapid relief that was maintained when evaluated two years after the start of treatment."
Professor Thomas' interest in cat allergy was sparked by biopharmaceutical firms using this type of allergy as their prototype for developing molecularly-based immunotherapy.
His research has focussed on how individuals respond to different cat allergens and how immune responses to different allergens can interact.
"It has the real advantage over house dust mite in that people allergic to cats can be made to develop symptoms by sitting them in a room with cats, thus providing a real-life assay where the time for development and the severity of symptoms can be measured," he said.
People had originally thought there was only one allergen.
"Our molecular cloning techniques were applied to define and produce three previously unrecognised allergens made by the cat salivary glands and to show that they were often important components in cat allergy.
"In collaboration with scientists at Circassia Ltd, we then demonstrated that their treatment with one allergen also changed the allergic responses to all the cat allergens - a not unexpected outcome from what immunologists call bystander effects - and this is encouraging for the uptake of the therapy."
The finding has had important applications in cold-climate regions where companion animals, and not house dust mites, are the major source of allergen for asthma.
Professor Thomas retired from being a research fellow of the National Health and Medical Research Council two years ago but still works as an honorary fellow at The Kids Research Institute Australia. He has continued to work with Associate Professor Hales to examine how the immune responses of asthmatic subjects to infections differ from those made by healthy subjects.
What's next?
Investigation of how changes in the microbiome and infections, such as the common cold, affect asthma will gain momentum.
The examination of new therapies with monoclonal antibodies against specific elements of immune system will take centre stage.
There will be more emphasis on the study of severe asthma using molecular techniques and genetics.
After the recent success of anti-cancer immunostimulants, similar smart immunostimulants will be investigated for allergy and asthma.
Methods and protocols to improve immunotherapy with both extracts and molecularly defined reagents will increase.
The continued use of microchips will make allergy diagnosis more accurate.