No one knows exactly what causes rheumatoid arthritis (RA), but researchers suspect that a combination of factors is involved. Hormones are thought to trigger the immune system to attack the joints and sometimes other organs. A virus or bacteria may also be at work. In recent years, genetics has proved to be a significant contributor to the disease.
Although scientists have yet to pin down exactly what role genetics plays, it has become increasingly clear that some people seem to have a genetic or inherited component that increases their chance of developing rheumatoid arthritis. What complicates the matter is that some people with rheumatoid arthritis do not have these particular genes. Others have these genes but never develop the disease. This somewhat contradictory data suggest that a person's genetic makeup can help doctors determine if a patient will develop rheumatoid arthritis, but they also prove that genetics is not the only factor. So far, researchers believe that many different genes appear to be involved, and each one, by itself, makes only a small contribution to one's susceptibility to the disease. How these genes interact is believed to impact one's individual disease risk.
Family Studies Support Genetic Link
Studies of families, as well as studies of identical and fraternal twins, further support the concept that inherited factors are important.
Investigators have already discovered that 2 to 3 percent of people who have a close relative with rheumatoid arthritis&mdashi.e. a parent, sibling or child&mdashwill eventually be diagnosed with the disease too.
Much of the research on families has been conducted by the North American Rheumatoid Arthritis Consortium. The consortium comprises researchers from 12 medical centers across the country. They have been carefully analyzing clinical findings and genetic material from 1,000 pairs of siblings who both have rheumatoid arthritis. By testing 400 different genetic regions, the researchers hope they can identify the specific genes associated with the disease. They also hope to pinpoint other genes involved in the spondyloarthropathies, an umbrella term for the class of arthritic conditions that affect the spine and other joints, as well as other rheumatic diseases.
So far, their research has confirmed an association between the development of rheumatoid arthritis and a cluster of genes involved in immune function called the human leukocyte antigen (HLA) complex.
HLAs refer to markers that influence the function of the body's immune system. The immune system uses the HLAs to differentiate self cells and non-self cells. A self cell is any cell that displays that person's HLA type and belongs to that person&mdashand therefore is not an invader. A cell that displays some other HLA type is non-self and is classified as an invader. HLA types are inherited. Some are thought to be connected to autoimmune disorders and other diseases.
Several decades ago, doctors made a significant discovery when a genetic link was identified between the HLA marker HLA-B27 and the arthritic class of diseases called spondyloarthropathies. Work is still underway to pin down the actual role of HLA-B27 in triggering the inflammatory response associated with the disease.
In the following years, scientists found that patients who are carriers of a group of genes known as HLA-DR have an increased risk of rheumatoid arthritis. The scientists have determined that four out of five people with this gene type appear to be at increased risk for the disease. Other genes also are suspected of being factors in the evolution of rheumatoid arthritis.
New research, announced recently at the 7th European League Against Rheumatism (EULAR) annual congress by researchers from Norway and the Netherlands, revealed that the presence of a gene called protein tyrosine phosphatase N22 (PTPN22) is associated not only with a patient's susceptibility to rheumatoid arthritis, but also to progression of the disease.
Finally, researchers have also recently announced that changes in a gene called runx1 appear to play a role in the autoimmune disease puzzle.
More Research is Needed
Despite these revelations, researchers need more data to establish the precise role of the genes already identified, and of other genes that appear to contribute to the immune response related to rheumatoid arthritis.
Identifying these genes is important because it helps to determine one's susceptibility for the disease. However, doctors are beginning to recognize that certain genes also correlate with how severe the disease will be. Finding out how they work and the role they play will provide a unique opportunity to use genetic markers as prognostic tools in the management of the disease.
One of the most exciting developments from this genetic research is in the field of treatment. As researchers continue to study the genetic patterns involved, they hope that one day they will be better equipped to develop therapies that disarm the genes' roles in the debilitating joint disease. Understanding how these genes work may also prove useful in designing diagnostic methods to identify the disease at the earliest possible stages.
For now, however, it is important to know if rheumatoid arthritis is in one's family history. That is crucial because even if the signs of rheumatoid arthritis have not yet started, their presence in a family member may signal one's predisposition toward developing the disease in the future.