Facts about rheumatic inflammatory diseases
Rheumatic inflammatory diseases are a collection of almost 100 disorders that are caused by inflammation of the movement organs or supportive tissue surrounding these organs, in other words the bones, muscles and tendons.
There are also rheumatic diseases that affect the entire body such as SLE (systemic lupus erythematosus) and myositis, as well as rheumatic diseases that are not caused by inflammation, such as osteoarthritis.
Rheumatoid arthritis most common
Rheumatoid arthritis affects 0.5-0.7% of the population and is the most common of the rheumatic inflammatory diseases.
Uneven gender distribution
Women are more likely to have rheumatoid arthritis than men.
Rheumatoid arthritis features inflammation of the membrane surrounding the joints. This causes swelling, tenderness, heat and stiffness in the body's joints, which are often affected symmetrically.
Untreated, the inflammation leads to the breakdown of cartilage and bone in the joints, which in turn causes limited mobility and misaligned joints.
Genes affect risk
A number of genes have been identified as increasing the risk of rheumatoid arthritis, most of which are involved in the immune system. Many are what are known as transplantation antigens which give rise to proteins whose role is to present foreign substances, antigens, to the immune system's T cells.
Smoking increases the risk for some
Smoking is the environmental factor that has, to date, been linked most strongly with an increased risk of rheumatoid arthritis, and increases the risk 20-40 times in people with certain genes. Occupational exposure to mineral oils has also been shown to increase the risk.
Autoantibodies present before symptoms
Rheumatoid arthritis involves the formation of what are known as autoantibodies - antibodies that turn the immune system against the body's own cells and organs - and these can be used when diagnosing the disease. The two most common are rheumatoid factor and antibodies to citrullinated protein antigens, ACPAs.
What role do the nerves play?
Jon Lampa is a researcher at the Department of Medicine, Solna and heads up a research group that is investigating nerve signals in rheumatism.
What have the nerves got to do with rheumatic inflammatory diseases?
"Recent years' research has identified a nerve mechanism that works very effectively on inflammation in the body. The nerve signals that pass along the tenth cranial nerve, the nervus vagus, suppress the activation of inflammatory molecules and cells.
The mechanisms behind this are well-documented for acute inflammation, but it's not clear what role they play in the regulation of chronic inflammation and pain mechanisms. This is what our research group is working on, particularly in the case of arthritis.
How can this benefit patients?
"Activating the nerve signals could be a new approach to suppressing chronic inflammation, and could be an important alternative to current drug treatments for rheumatoid arthritis and other inflammatory disorders."
How does treatment affect the risk of cancer?
Johan Askling is a researcher in epidemiology at the Department of Medicine, Solna.
Does the risk of cancer increase for patients treated with TNF-alpha inhibitors?
"Our data so far doesn't show a marked increase in the incidence of cancer, but there is a need for structured long-term monitoring of the newer and more potent drugs such as TNF-alpha inhibitors and other biopharmaceuticals. More and more of our patients are being given these treatments, but the long-term effects and side-effects are not entirely clear."
Are more studies needed?
"Yes, but they're not without their challenges - large groups of patients have to be monitored for long periods to capture the risk of rare side-effects. Control groups with patients who are very similar to those being treated must also be identified and monitored for the same length of time.
We have set up a register, ARTIS, that follows all patients treated with biopharmaceuticals which, combined with other national Swedish health data registers such as the Cancer Register, make for an internationally unique opportunity for studying cancer risks and any other side-effects.
What is the role of the immune system?
Vivianne Malmström is a researcher in immunology at the Department of Medicine, Solna.
How can knowing more about the immune cells help future patients with rheumatic inflammatory disorders?
"Many, but not all, patients with rheumatoid arthritis have antibodies to one of the body's own proteins, known as citrullinated proteins. Their immune system has been activated as though citrulline were foreign and dangerous. If we could prevent this reaction, we'd be able to cure rheumatoid arthritis, whereas today we can only alleviate it.
We're using cellular immunological methods to try to get to the bottom of the immune reactions to citrulline that lead to rheumatoid arthritis.
We're studying autoreactive B and T cells, in other words the immune cells that react to the citrullinated proteins. The aim is to come up with a treatment that specifically affects these cells and not other parts of the immune system that are needed to fight infection and so on."
Advances in medicinal treatments
Prior to 2000 a new treatment for rheumatic inflammatory diseases came along roughly once every 20 years. However, since then around ten new drugs have been launched in a short time, all of which are based on the major molecular breakthroughs of the 1980s and 1990s on key molecules in the inflammatory process and biotechnological advances in creating targeted biopharmaceuticals that work against these molecules.
Gold salt: Injected into the joints for rheumatoid arthritis to alleviate inflammation. In 2008 researchers at Karolinska Institutet showed that the immune system's macrophages stop secreting the inflammatory protein hmbg1 when cultured with gold salt.
Sulfasalazine: Devised by Nanna Svartz, professor at Karolinska Institutet.
The 1950s brought the advent of cortisone.
Chloroquine: An anti-malarial that also proved to be effective against rheumatic disorders.
Methotrexate: A cell growth inhibitor whose mode of action on rheumatoid arthritis is unclear.
2000 and beyond
TNF-alpha inhibitors, interleukin receptor inhibitors and other biopharmaceuticals. All inhibit very specific molecules in the inflammatory process, and are produced from proteins taken from living humans or animals.
Text: Cecilia Odlind. First published in the magazine "Medical Science", number 3, 2010