The immune system is there to protect us from threats and infections. But to be healthy, it also needs to be tolerant of an individual’s own tissues that are harmless. If it can’t do this, the immune system does the very opposite of what it’s supposed to do – attacking rather than protecting us.
There are more than 80 of these types of disorders, including type-1 diabetes and Rheumatoid arthritis. In autoimmune diseases such as Multiple Sclerosis (MS), the immune system mistakenly recognises parts of proteins, known as antigens, belonging to the body’s own organs and mounts a destructive immune response against them. In MS, damage to the central nervous system causes a range of neurological problems that can include movement, speech and memory problems.
There are a wide range of strategies for treating people who have autoimmune diseases. Unfortunately, none can cure the diseases and many involve suppressing the immune system, which can have side-effects, making patients more susceptible to infections.
From aggressive to protective
David Wraith’s group at the University of Bristol, which I am part of, has been working on ways to restore immunological tolerance – the normal, unresponsive state in healthy people – to patients with autoimmune disease. And in a new study, published in Nature Communications, we’ve shown that immune cells can be stopped from attacking healthy body tissue and even convert them from being aggressive to actually protecting against the disease.
By targeting the specific immune cells that cause autoimmune disease we can “switch off” their automatic reaction but, crucially, without compromising normal immune function. To do this, we used antigens that are normally the target of the immune attack. This re-educates the aggressor immune cells, and prevents them from attacking the body’s tissues. We found that during this antigen-specific immunotherapy treatment, aggressor cells actually convert to become anti-inflammatory cells which actively suppress autoimmune disease.
Because this is done without compromising other parts of the immune system, patients are still able to mount immune responses that protect them from infections.
Our study shows that immunotherapy can be made safer and more effective by gradually increasing the dose of antigen administered at each stage of treatment, improving the conversion of aggressor cells to protector cells which prevent autoimmunity.
We also wanted to know what effect treatment had on the activity of genes at each stage that the treatment dose was escalated, to understand exactly how aggressor cells change. By looking deeper, we saw a switch from the activity of pro-inflammatory genes towards dominance of anti-inflammatory genes. This provides a wealth of information on how disease-causing immune cells are re-educated to become protective cells. Understanding this will allow researchers to further manipulate the immune system even more effectively to prevent autoimmune disease.
Valuable new markers will also allow scientists to gauge the effectiveness of this antigen-specific immunotherapy treatment in patients. Collectively, these discoveries have important implications for the many patients suffering from autoimmune diseases that are currently difficult to treat.
The research forms part of a number of experimental treatment strategies that we’re exploring, which we hope will contribute to improving the lives of millions of people worldwide and this therapy for MS patients is currently undergoing clinical development through a University of Bristol spin-out company.
MS alone has 2.5m sufferers worldwide but if you include all autoimmune diseases then the number is much higher. We have hopefully taken another small step towards a cure.