Rituxan® Being Studied as a Possible Treatment for Lupus
American College of Rheumatology 2006 Annual Meeting, Plenary Session III, November 14, 2006, Presentation 1974
B Cell reconstitution after rituximab recapitulates B cell ontogeny with a preponderance of transitional B cells and a paucity of memory B cells
B cells, a group of white blood cells, play a number of important roles in the body’s immune system. After their creation in the bone marrow, B cells go through several transitions before they are equipped to take on specific roles. Some B cells, called memory B cells, recognize and target foreign invaders, such as germs or viruses, that need to be destroyed and removed to prevent disease; memory B cells can survive a very long time, circulating in the blood and lymph tissue. Other B cells produce specific antibodies, which are the proteins that assist in destroying and removing these foreign invaders as well as older or diseased cells.
Since increased or abnormal B-cell activity may be a factor in lupus and other autoimmune diseases, several forms of treatments for autoimmune conditions involve reducing the number of a patient’s B cells; and that is how the medicine rituximab (Rituxan®, developed by Genentech) acts. Rituximab has been approved for the treatment of rheumatoid arthritis, and is currently in clinical trials to see if it could be useful for lupus patients as well.
Though B-cell depletion with rituximab has been used for a number of years, questions remain about its long-term effects on the immune system. Jennifer Anolik, MD, and her colleagues at the University of Rochester Medical Center looked for clues at the B cells that come back in the bone marrow after the initial depletion by rituximab therapy, noting differences in the kinds and functions of the replacement B cells in patients treated with rituximab compared to patients who did not undergo B-cell depletion.
Their research indicated that during the period when the B-cell population was being reconstituted, a large number of the new B cells remained in a transition phase (sort of like adolescence, in which they were not premature, but not quite mature either), and thus were unable to participate in the immune response. This finding was similar to what happens to the immune system after bone marrow transplantation. They also pointed out that lupus patients who remained well for a very long time had more transitional cells and fewer mature cells such as memory and antibody-producing B cells.
These early findings have potentially very important implications for lupus patients and other patients who are treated with B-cell depleting medicines. Because their immune systems might have fewer mature cells capable of mounting a response to bacteria and viruses, they will need to be monitored closely for the risks of infection; it may even have an impact on their ability to receive vaccinations.
On the other hand, the fact that lupus patients who were disease-free for years had a B-cell profile that resembled those following B-cell depletion suggests that there may be ways to change the makeup of the immune system cells that may also fundamentally alter the autoimmune disease process. That could potentially lead to longer-term benefits, although more studies are needed before it is known if that will actually happen.
Connect with Us: