Rheumatoid Arthritis: Immunological Factors

Rheumatoid arthritis is an autoimmune disease which occurs when the immune system creates an unwanted response that targets the body's tissues and organs.

Normally, a healthy immune system counts on tiny white blood cells that circulate throughout the body to protect it from viruses, bacteria, cancer cells, toxins and other foreign invaders. The presence of the foreign substances, or antigens, activates the white blood cells to mount an immune response that entails recognizing and destroying the invaders that can cause the body harm.

Differentiating Between T cells and B cells
Trillions of white blood cells carry out this important task. The two major classes are called T cells and B cells.

T cells work in two ways. They attack, surround and essentially disarm the invaders. They also direct and regulate the body's immune response.

In autoimmune diseases, something triggers the body to mount an abnormal immune response, including the stimulation of T cells and the production of antibodies. As a result, the immune system begins attacking the very cells, organs and tissues in the body that it is supposed to protect. In the case of rheumatoid arthritis, the cells set off a reaction that causes inflammation to occur in the lining of the joints, also known as the synovium.

The B cells work primarily by releasing specific antibodies into the body's fluids. The antibodies then ambush the antigens and pave the way for T cells to do their job.

One of the antibodies produced by B cells is called rheumatoid factor. Research indicates that people with high levels of rheumatoid factor may have a malfunctioning immune system. That explains why doctors often request a test that measures the level of rheumatoid factor when trying to diagnose rheumatoid arthritis. In general, the higher the level of rheumatoid factor present in the body, the more severe the disease activity is likely to be.

However, not all people with rheumatoid arthritis have an elevated rheumatoid factor, and not all people with an elevated rheumatoid factor have rheumatoid arthritis. The test can also come out negative if it is done too early in the course of the disease. Approximately 20 percent of people with rheumatoid arthritis will have a negative rheumatoid factor test and some people who do not have rheumatoid arthritis will test positive.

The Role of Cytokines
Another essential part of the immune response takes place when white cells secrete substances or proteins known as cytokines. These proteins serve many roles. They encourage cell growth and spark cells to activate. They also communicate messages to cells.

In the over-stimulated immune system, cytokines tell cells to reproduce and mature at a much faster rate. In effect, the cytokines are causing the activation of additional T cells, which releases more cytokines, perpetuating the cycle of damaging inflammation.

In the case of rheumatoid arthritis, the cytokines build up in the synovium, which draws in more inflammatory cells and results in painful swelling of the joints, hands and feet. Excessive amounts of these damaging cytokines can lead to inflammation in other body tissues as well such as the tendons, cartilage, eyes, heart, lungs and kidneys.

Cytokines Responsible for Joint Damage
Two specific cytokines have been linked to rheumatoid arthritis. They include interleukin-1 (IL–1) and tumor necrosis factor-alpha (TNF-alpha). Both send inflammatory messages to other cells that help fuel the overall immune response that leads to inflammation and joint damage, and both have been found to be abundant in the synovial lining of the joint.

The presence of these cytokines is believed to lead to joint deterioration and erosion of the cartilage that is the cushioning material at the end of bones. Their presence also causes swelling of the synovium. The joint damage results as the cartilage wears down and the space between the bones narrows. If the condition worsens, the bones start to rub against each other. If the joint lining expands, it can invade into or erode the bone and can eventually lead to irreversible bone damage.

Novel Treatments Target Cytokines
As doctors learn more about how the immune system functions and the specific cytokines responsible for the progression of disease, they have been better able to both target the mechanisms that cause specific immune responses and develop novel therapies that zero in on this aspect of the disease.

Already, they have made significant progress in determining how best to seek out and destroy harmful immune cells while leaving other parts of the body's disease fighting system intact. A class of medications known as biologics has shown promise in their ability to seek out and destroy certain cytokines. Biologic treatments already on the market block the production of TNF-alpha and IL-1.

A new class of medications called co-stimulation modulators were recently approved to treat rheumatoid arthritis by inactivating the T cells that stimulate the inflammatory response.

More attention is being focused on B cells as well. A monoclonal antibody called Rituxan (rituximab), which has typically been used to treat cancer, was recently approved for the treatment of rheumatoid arthritis. It targets and reduces the number of B cells in the body, which are believed to play a role in the initiation and development of the disease.

Researchers are also looking at the role played by other cytokines. For example, a new therapy is aimed at blocking interleukin-6 (IL-6), another protein found in excessive amounts in the joints of people with rheumatoid arthritis. It is also believed to be responsible for joint damage and swelling. Investigators now surmise that IL-6 may be a cause of fever and excess blood platelets (thrombocytosis) in people with rheumatoid arthritis. Researchers hope that blocking IL-6 can reduce its damage and early research has shown promise.

In the future, researchers may discover that other cytokines are also at work in the deterioration caused by rheumatoid arthritis. For example, it is possible that the cytokines that normally suppress inflammation are missing or are present in low numbers. Scientists may one day develop biologic medications that boost their levels to rebalance the immune system and restore it to its normal purpose.

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