Why in some immune-mediated diseases does the immune system mistake parts of the body as foreign invaders? What triggers it? These are important questions, and they are being asked not just for MS, but for a number of different diseases, including diabetes, arthritis, Graves’ disease and lupus, to name just a few.
MS arises when the immune system attacks the myelin sheath, an insulating coating on nerve fibres. This attack damages the insulating coating which disrupts or halts the signals travelling down the nerves, interrupting the signaling between the brain and the body. Given that the brain controls everything we do, this disruption can result in a wide range of symptoms.
Every second you are alive your immune system is constantly making decisions. Most of the time when it encounters something new, it is likely to be harmless, but there is a small number of times when it will come across something that is very dangerous. The immune system must be able to discriminate between the two scenarios while also distinguishing between self and non-self. Most of the time it gets it right and we can survive in an environment full of bacteria and parasites. But unfortunately, sometimes this goes a little askew.
Australia has led the way in terms of research into understanding some of the environmental risk factors that might lead to MS. If these factors influence our risk, they must also influence the immune system. These factors include genetics, vitamin D levels, UV light exposure, EBV infection and some others (for a more comprehensive article on risk factors, you can read here).
While a number of risk factors have been identified, the actual molecular mechanism has not been discovered. We know that events occur that cause the immune system in MS to go awry and hence many of the successful medications used to treat MS target the immune system. However, despite a number of attempts, an autoantibody has not been discovered in people with MS, which means that MS doesn’t meet the criteria to be classified as an autoimmune disease, but rather falls under the category of immune-mediated diseases. An autoantibody is an antibody (a protein) produced by the immune system that is directed against one or more of the individual’s own proteins.
Scientists at the Garvan Institute of Medical Research in Sydney have recently published a scientific study in the prestigious journal Cell which might help unlock some of the mysteries behind the molecular mechanisms generating auto-reactive immune cells.
Using cutting edge genetic technologies, the researchers looked at a small number of people with Sjogren’s syndrome. Sjogren’s syndrome is an autoimmune condition that mainly affects the eyes and salivary glands. They analysed some of the autoantibodies in these individuals and traced them back to the B cell (a type of immune cell) that made these antibodies. They then analysed the genetic makeup of those cells to try and determine why they exist and how they had gone awry.
What they found was that the cells that produced a response against the body had accumulated mutations in their DNA, which shared similarities to mutations found in lymphoma (a type of cancer arising from immune/blood cells). It is important to note that these cells weren’t cancerous, but they probably had lost some of their ability to control their rate of growth and also lost some of their ability to repair mistakes in their DNA. These mutations turn these cells rogue, allowing them to evade immune tolerance checkpoints that should destroy any cells that attack the body. It also allowed them to multiply unchecked, leading to a small number of out of control immune cells, producing some of the auto-reactive antibodies in these people with Sjogren’s syndrome.
While this study has been carried out in a different autoimmune condition, it may be similar to what occurs in MS. MS Research Australia works closely with other organisations in other disease areas to ensure we can leverage off each other’s understanding and research.
To date, studies like this have been technically unfeasible, as these rogue cells are rare, possibly only 1 per 500 normal immune cells. Traditionally, the only way these studies could be done was via collecting pools of cells which would have masked the rare cells. It is only through advances in DNA technologies that has allowed the analysis of individual cells. It is an exciting time in research that such things can be discovered, and we look forward to similar studies being carried out in MS.