New understanding of HLA-mediated susceptibility and protection in a rare, autoimmune renal disorder may help deliver new therapies for more common autoimmune diseases such as type 1 diabetes, multiple sclerosis and Crohn’s disease.
Australian-led research published in Nature identified Goodpasture’s disease as a simple ‘model’ of autoimmune disease. It has a single dominant autoantigen within type IV collagen and the HLA associations are well described, with HLA-DR15 conferring an increased risk of disease and HLA-DR1 being protective.
Co-senior author Professor Richard Kitching, director of the Monash Centre for Inflammatory Diseases, said DR1 is dominantly protective against Goodpasture’s disease in the presence of DR15.
“In Goodpasture’s disease when the molecule DR15 is present it can select and instruct T cells to attack the body,” he told the limbic. “But when people also have the protective DR1 molecule, these T cells are held at bay and can be overturned.”
Professor Kitching said their study showed DR1 can generate epitope-specific regulatory T cells, which help suppress the autoreactive cells.
They identified structural differences in the DR15 and DR1-alpha3135-145 peptide complexes that change the way the immune system ‘sees’ the autoantigen and are critical to the way the immune system selects antigen specific T cells.
“We have known that in autoimmune diseases there are T cells that make us susceptible to disease and T cells that protect us from disease. Now we know how this happens, it opens the field for new and more targeted treatments to specific diseases.”
He said the regulatory T cells were highly specific – suggesting that they could be used as a more potent and less toxic treatment. In contrast, most current treatments for autoimmune disease are non-specific, affect protective immunity and have significant metabolic effects in patients.
“So, if we can encourage these regulatory T cell to develop in the body, or expand people’s cells outside the body and inject them back into those with disease, this could result in better and more targeted treatments for autoimmune diseases.”
While the specific epitopes and peptides responsible in other autoimmune diseases such as type 1 diabetes will be different, Professor Kitching said their findings on the underlying mechanism of protection in Goodpasture’s disease may be relevant to these diseases.