Lupus, or systemic lupus erythematosus — SLE for short — is a devastating disease in which you produce antibodies that attack your cells and your tissues. This so−called autommune disorder can affect the joints, kidneys, heart, lungs, brain, blood and skin. It is chronic, staying with people throughout their lives and flaring up unpredictably.
Joint aches, fever, fatigue, and skin rashes are among the most common symptoms of lupus. Because these symptoms have so many possible causes and because they tend to vary from person to person and from time to time, SLE is often misdiagnosed even though it is fairly common, affecting about 1.5 million Americans, particularly adult women and African Americans.
No one knows exactly what causes SLE or why some people get it and others don't. It is thought to have a genetic component and is not contagious. As medical science learns more and more about how the disease works, there is increasing hope for better and safer drug treatments.
SLE is often misdiagnosed even though it is fairly common, affecting about 1.5 million Americans, particularly adult women and African Americans.
The immune system is made up of a vast array of different kinds of cells. We know that SLE particularly affects one part of the immune system -- B cells. B cells identify viruses, bacteria and other threats to the body's health and then produce antibodies to attack and destroy those specific invaders. SLE causes B cells to become hyperactive and produce antibodies to healthy tissue. This leads to different kinds of damage, depending on which systems and organs are affected by the antibodies.
Because these therapies, especially high-dose steroids and cytotoxic drugs, suppress the entire immune system, they can leave the body vulnerable to serious and even life-threatening infections. Not everyone is helped by these drugs. Some SLE sufferers respond poorly or not at all.
We know that SLE particularly affects one part of the immune system, B cells. B cells identify viruses, bacteria and other threats to the body's health and...produce antibodies to attack and destroy... invaders.
Two categories of drugs currently under study are designed to target B cell activity and leave the rest of the immune system to protect the body. One of these, B cell-depleting drugs, reduces the number of B cells and interferes with the functioning of those that remain. The other, called an anti-cytokine drug, blocks the action of B cell-stimulating cytokines, proteins within the immune system that regulate B cells and other parts of the immune response. Let's take a look at these studies and what they tell us about these two categories of drugs, so far.
Both rituximab and epratuzumab have the advantage of reducing the number of B cells without affecting other cells that play a key role in the immune system.
A second study of lupus patients treated with rituximab or rituximab and cyclophosphamide for four years found that after 19 months, patients' fatigue, joint pain, arthritis, serositis, kidney problems, thrombocytopenia (lowered blood platelet count) and anemia all improved. During nine months of follow-up, no serious infections developed.
Another trial of rituximab, used along with other drugs, found that of the 17 SLE patients who completed the study, 11 achieved a significant reduction in B cells and all showed improvement in two to three months which lasted twelve months or more. Seven people in this study suffered from kidney inflammation caused by SLE. One of these improved to the point of a complete return to normal kidney function. None of the group died or had any serious infections.
In a separate pilot study, rituximab was given to 11 people who had not been helped by conventional immunosuppressant drugs. All 11 received infusions of rituximab along with methylprednisolone, a steroid. Eight of the 11 completed the infusions and 6 of these saw a dramatic reduction in their B cell count and significant improvement in SLE symptoms. Two went into long-term remission.
Lupus can sometimes attack the nervous system producing headaches, seizures, depression and stroke. Scientists have named this disorder neuropsychiatric lupus. Rituximab also shows promise in controlling this disorder, one of the most serious and difficult to treat forms of SLE.
Another area of concern is the effect of these drugs on children with SLE because the drugs (particularly rituximab) significantly lower children's immunoglobulin levels, the antibodies needed to fight infection. Giving children IV immunoglobin may solve this problem.
Bit by bit we are making progress in our efforts to understand and treat lupus/SLE. Along the way we may also find the key to dealing with other autoimmune diseases. Drugs designed to reduce B cell activity by reducing the number of B cells themselves have shown the most promise. Even though the results so far have not been encouraging regarding the usefulness of drugs to control the cytokines stimulating B cells, this research is still in its infancy.