This article describes the use of biologicals to halt the production of specific B-lymphocytes involved in the development of autoimmune diseases.
Biologicals are a broad class of chemical compounds that have a biological, that is, an animal or human origin. Most biologicals have traditionally been used to induce immunity to infectious agents or noxious substances of biological origin. With advances in molecular biology, this has changed. Today's biologicals include immune serums, antitioxins, vaccines, and a number of therapeutic agents including monoclonal antibodies. In patients with autoimmune diseases biologicals, primarily monoclonal antibody therapies, offer a wide range of benefits.
The first biological therapies were introduced in 1997 when a B-lymphocyte cell depleting monoclonal antibody was developed to reduce B-lymphocyte production in patients with B-cell lymphoma. Monoclonal antibodies target specific substances, in this case B-lymphocytes.
B-LYMPHOCYTES
Lymphocytes are a type of mononuclear white blood cell. Lymphocytes are the key players in the immune system. Lymphocytes help protect us from infection and they help us heal when we develop infection.
There are two primary classes of lymphocytes: T cells and B cells. T cells scout for infectious and toxic agents. When they encounter infectious agents, T-lymphocytes launch an attack by triggering the production of antibodies that target these agents.
B-lymphocytes are immune system cells that produce antibodies. The production of specific antibodies by B-lymphocytes in under genetic control and it is under T-cell influences. For instance, if we're exposed to a hepatitis virus, our immune systems produce antibodies that neutralize or destroy the hepatitis virus. This helps us recover from infection and it provides immunity the next time we're exposed to hepatitis.
VACCINES
Vaccines can be either active or passive. In active vaccinations, we're inoculated with a small amount of the inactivated infectious agent. Our immune system responds as if we were infected with the agent and it produces antibodies that confer immunity. That is, if we're exposed to the infectious agent, these antibodies will launch an attack and prevent us from developing the particular infectious disease.
In passive vaccines, such as the HBIG vaccine for hepatitis, we're injected with a solution containing hepatitis B antibodies. This offers protection from infection with hepatitis B for several months. Because it takes several weeks before we produce sufficient antibodies from active vaccines, we would be given a passive vaccine if we were exposed to a substance for which a passive vaccine was available.
MONOCLONAL ANTIBODIES
Just as we produce specific antibodies to the specific infectious agents that we encounter, monoclonal antibodies are produced to react with specific substances. Certain monoclonal antibodies, such as rituximab, target specific types of B-lymphocytes that are known to cause the develop of certain autoimmune diseases. Specifically, these B cells have specific surface markers associated with the production of certain autoantibodies. By reacting with monoclonal antibodies in therapy, these B-lymphocytes aren't available to produce the autoantibodies associated with certain specific autoimmune diseases.
Monoclonal antibody therapy is a hot topic among autoimmune disease researchers. Drugs such as rituximab, epratuzamab, and belimumab are some of the most promising agents. The major side effects arise from the specific action of monoclonal antibodies. For instance, monoclonal antibody therapy for multiple sclerosis, with reduces production of myelin basic protein antibodies, is associated with the development of thyroid autoantibodies and the development of autoimmune thyroid disease.
Researchers are focusing on ways of making monoclonal therapy more effective. New laboratory tests are being developed that can accurately detect changes in the levels of specific B-lymphocytes or other markers of disease activity. These results could then be used to evaluate improvement or remission from disease.
Resources:
Robert Eisenbert, Targeting the B Cell in Autoimmune Diseases, InFocus Newsletter of the Autoimmune Diseases Association, Vol 14, No. 3, Sept 2006.
Elaine Moore, Autoimmune Diseases and Their Environmental Triggers, McFarland and Company, 2002.
