A University of Queensland team at the Princess Alexandra Hospital is believed to be the first in the world to find a mechanism to turn off an auto-immune disease, once it has started.
The work, published today in Immunity, provides a possible basis for a vaccine against auto-immune diseases, including rheumatoid arthritis and juvenile diabetes, where the body`s immune system inappropriately attacks healthy cells.
The work, which is still at the preliminary stages, also has implications for treating allergic diseases such as asthma, and making allografts safer.
However, a commercially available vaccine is several years away, with human clinical trials yet to be held. Although a cure is not yet available, the UQ team believes it is making excellent progress.
The UQ Centre for Immunology and Cancer Research team at Princess Alexandra Hospital found a molecular control mechanism to re-educate the immune system.
"It`s not a new idea to re-educate the immune system," said academic rheumatologist and Centre Deputy-Director Associate Professor Ranjeny Thomas.
"What`s different is that this is the first time it has been possible to suppress an existing response once the immune system has started down a deleterious pathway."
Dr Thomas and her UQ team including Dr Ela Martin, Dr Brendan O`Sullivan, and Ms Pauline Low made the new discovery while working on dendritic cells, which are potent, antigen-presenting cells with the unique capacity to prime the immune response.
She said many research groups internationally were exploring the properties of dendritic cells, but with considerably different scientific approaches.
Dendritic cells are found in lymphoid organs as well as non-lymphoid tissues, including the skin, joints and circulating blood.
Dr Thomas said suppression of a previously primed immune response was a major challenge for immunotherapy of autoimmune and allergic diseases. The team achieved success by exploiting their understanding of the pathway controlling the interaction between dendritic cells and the immune system.
The team turned off, one of the key molecules in dendritic cells which feeds through to the T-cell immune response. They suppressed RelB activation in mouse and human dendritic cells, with the aim of suppressing or tolerizing the immune system.
Preliminary findings suggest that autoimmune disease can be treated with dendritic cells to provide antigen-specific immune suppression.
"These observations have wide future implications for antigen-specific therapy of autoimmunity, allergy and allografting," Dr Thomas said.
Rheumatoid arthritis (RA) is a debilitating condition which affects one in every 100 people.
In RA, the immune system inappropriately attacks joints as if they were made of foreign proteins, eating away at the cartilage and damaging the underlying bone. RA affects three females to every one male contracting the condition.
Symptoms include pain, swelling of joints, and later deformity and loss of function in hands, knees and other joints.
"Most auto-immune diseases have their onset when people are aged in their 20s to 40s, and they last a lifetime," Dr Thomas said.
"Although RA currently is not curable, treatment protocols have greatly advanced in the past 10 to 15 years, with many patients achieving remission on drugs."
The team has patented pre-clinical models of the vaccine through the University`s technology transfer company, UniQuest.
Dr Thomas said the UQ team would not try to do all the work on all auto-immune diseases themselves, but would seek pre-seed funding to develop their system and concentrate on a few areas including arthritis, an area in which they specialised.
They would also work with research groups in Australia and internationally in other auto-immune disease areas. In Brisbane, the team is collaborating with another team at QIMR to test the system for graft vs host disease.
Dr Thomas has gained an international reputation for her work on dendritic cells in rheumatoid arthritis and developed methods to alter the function of dendritic cells.
The Dendritic Cell Biology group she leads at the Centre for Immunology and Cancer Research has also recently completed phase II clinical trials using a dendritic cell vaccine for melanoma.
Dr Thomas said the Centre had set up a website for people with questions about the project, who wished to provide financial support, or who wished to register their interest in taking part in any future trials. It can be viewed from www.cicr.uq.edu.au
Although it has been many years in development, the project itself has
received Arthritis Foundation of Queensland and National Health and Medical
Research Council (NHMRC) funding.
© The University of Queensland, Brisbane