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Immunology research: At the heart of studying arthritis

Published on 18 April 2013
Source: Arthritis Today

Dr Natalie Carter looks at the vital role played by our immune systems in treating inflammatory arthritis.

Introduction to immunology:

We all know that having a strong immune system is important for our wellbeing. We see many messages from advertisers of yoghurt drinks, vitamins and foods telling us that their products can help us to achieve this. In this article I hope to explain what the immune system is and why we at Arthritis Research UK are so interested in studying it and understanding how it works.

Immunology is a very powerful word. It is seen as a dark and complex science that is incredibly difficult to understand. Of course, it is complicated but our researchers are now able to shine a light on how our immune cells contribute to arthritis and also how they can be harnessed to develop new therapies.

Immunology: the fundamentals

Our immune system is a very powerful set of tools that is designed to protect us from invading organisms that can cause disease- these are sometimes called pathogens. These include bacteria, such as Salmonella, viruses like influenza, as well as more exotic things like parasites, worms and fungi.

We already have some basic protection from these pathogens from the barriers our body puts up. For example our skin provides a barrier, our tears contain special enzymes that can help to prevent eye infections and our stomach contains acids which help to kill any nasties (like mould or bacteria) from our food. However, pathogens have been waging war with us for over six million years and so have many ways to bypass these barriers. If a pathogen manages to breach our barriers, it enters our circulation, where, if left unchecked, it can divide and multiply, causing havoc. Our immune system has to step in before this happens.

The immune system has two lines of defence. The first is a rapid response designed to stop pathogens in their tracks as fast as possible. Our second line of defence, is slower to respond but can provide an exquisitely specific response. It is this part of the immune system that gives us ‘immunological memory’; this is when the immune system remembers a pathogen that has been encountered on a previous occasion and is able to mount a fast-paced, devastating attack. This is why we only get chicken pox once and are then protected from this disease for the rest of our lives.

Why should we study immunology?

It sounds like a fantastic system for preventing infection, and it is. But like most things in life, it is far from perfect. Sometimes we get ill; we can catch winter flu because the flu virus has mutated, modifying the cell surface and preventing our immune system from recognising it. Although this can make us feel miserable, we normally recover. For other people the immune system can go seriously awry and start to attack their own body, causing major problems.

When our immune system attacks our own tissues, this is called autoimmunity. Autoimmunity is the underlying cause of a wide range of conditions including lupus, rheumatoid arthritis, Sjögren’s syndrome and vasculitis. Some autoimmune conditions affect a single organ or tissue and some are systemic, possibly affecting the whole body. An example of a single organ disease is type I diabetes where antibodies are produced against insulin cells within the pancreas. This results in these cells being destroyed, so that patients are unable to make their own insulin. An example of a systemic disease is systemic lupus erythematosis (SLE). Here many organs are affected including the skin, brain, heart and joints.

The basis of treatments for autoimmune diseases is often to try and dampen down this abnormal immune response. Treatments to restrain the overactive immune system can include steroids, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive drugs such as azathioprine and cyclophosphamide, and biological therapies like anti-TNF.

Arthritis Research UK-funded research

Arthritis Research UK funds many projects where our scientists and clinicians aim to unpick the cells responsible for autoimmunity in rheumatological conditions. For example, Professor Rizgar Mageed at Queen Mary University of London, is working on a specialised type of cell in our immune system called B cells.

Professor Mageed is interested in the role of B cells in lupus patients, and aims to identify the specific set of B cells that can cause severe lupus. Rather than acting as protectors, B cells can attack the tissues of patients with lupus and cause damage to otherwise healthy tissue. This produces a range of symptoms such as inflammation of blood vessels, skin rashes and arthritis. Professor Mageed and his team want to investigate how B cells cause and influence lupus and so help design more effective treatments.

One possible treatment for lupus is to use a drug called rituximab. This drug is designed to remove all B cells – including the ones that contribute to symptoms such as skin rashes and kidney damage. However, as B cells are an integral part of the immune system, this means that one side-effect of the drug is that patients have a compromised immune system. Professor Mageed has identified some autoimmune B cells in people with lupus that do not seem to be present in people with other autoimmune diseases. Therefore by targeting these cells there would be a unique opportunity to knock out the cells causing lupus whilst leaving the other elements of the immune system untouched. This is one of the ‘holy grails’ of rheumatology – instead of dampening down the whole immune system, leaving the patient prone to infections, we could target the specific, disease-causing cells. Professor Mageed’s work provides the fundamental information we need to design better, more specific and more effective treatments for autoimmune disease.

Wider implications:

The relevance of immunology is not restricted to autoimmune conditions. Now that we have a deeper understanding of the immune system, we can see it in action in many other arthritic conditions. Attitudes towards osteoarthritis are already changing. This common condition has traditionally been seen as wear and tear of the joint as we get older. We now understand that this is only part of the story. It is true that our risk of developing osteoarthritis increases as we get older. However, our immune system has an important part to play as well. We now know that one feature of osteoarthritis is the infiltration of immune cells into the joint, which causes inflammation. As a result of this new knowledge, we are investigating the use of drugs traditionally used to treat inflammatory arthritis, such as methotrexate and hydroxychloroquine, in osteoarthritis.

Dr Natalie CarterFurthermore, there is also some tantalising evidence to suggest that immune cells, and the molecules they secrete, can have a potent effect on how we experience pain. If proven, this would suggest that disease-modifying anti-rheumatic drugs (DMARDS), such as methotrexate, could play an important role in pain relief, as well as affecting the immune system. Altogether this places the immune system at the heart of Arthritis Research UK’s mission to research into the cause, treatment and cure of all forms of arthritis.

Dr Natalie Carter is Arthritis Research UK’s scientific liaison manager

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