Juvenile Idiopathic Arthritis (JIA) is the most common disease of the joint, muscle and ligaments in children. It is characterised by joint swelling that lasts at least six weeks. We now know that early intensive treatment of JIA reduces the risk of long-term joint damage and increases the likelihood that arthritis will be sufficiently controlled to allow treatment to be stopped in the future. This suggests that a ‘window of opportunity’ exists in the early stages of disease where effective treatment may have a greater long-term impact on disease severity. Importantly, not all types of arthritis are the same.
While some children with JIA already have severe arthritis at the time of diagnosis, many have mild disease. Over time, some of these children will go on to develop severe arthritis, while in others, the arthritis improves with only simple medications such as ibuprofen. At present, we cannot predict which children will go on to develop severe arthritis and therefore, more targeted drugs are only commenced when the arthritis has already spread to involve other joints.
Joint inflammation (the process by which the body’s own immune cells leave the bloodstream and enter the joint resulting in pain and swelling) occurs within the lining of the joint, called the synovial tissue. We have pioneered the use of a safe and well-tolerated method to obtain small pieces of the synovial tissue in children. We have combined this technique with new technologies that allow us to examine all the different types of cells in the synovial tissue. This includes both specialised cells that form the lining of the joint and immune cells that have passed from the blood into the synovial tissue. Through this technique, we have gained remarkable insights into which cells are ‘good’ and reduce inflammation and which are ‘bad’ and make inflammation worse. However, cells do not exist as single units, but instead collaborate and communicate with immune cells entering the tissue. We have found that cells that reside in the tissue create an environment that supports the ‘bad’ behaviour of certain immune cells in the tissue. We propose that detection of these areas in the tissue could help us identify those children whose arthritis will become severe.
We now aim to use our existing data and analyse synovial tissue samples obtained from the inflamed joints of children with JIA at the time of diagnosis, to see if we can find differences in how these cells organise themselves in the tissue of those children with mild arthritis at diagnosis who then develop severe arthritis (extended oligoarticular JIA) compared to those that do not (persistent oligoarticular JIA) or those who have severe arthritis from the start (polyarticular JIA). This information is crucial to developing new treatment approaches that selectively target children at risk of developing severe arthritis before their disease has spread to other joints. Consequently, this will enable the use existing treatments earlier, more effectively and allow us to develop new drugs specifically targeting the cells causing severe arthritis. The ‘right drug’ to the ‘right child’ at the ‘right stage’ of their arthritis.
We have recently overcome this barrier in the MAPJAG study in which we have pioneered the application of biopsy techniques to obtain small samples of synovial tissue from inside of the joint, at the same time as routine joint injections.
