Leading the way to a cure

Lupus Research Update: 2007 Volume 1

Volume 1, 2007 - Online Edition | In This Issue

The results are in! >
ALR's 2007 grant recipients >
One Love. One Cause. ALR Gala a Smashing Success >
The Faces of Lupus >
Advocacy Update — ALR Goes to Washington >
Research Results - Rituximab Results in Long-Term Immune Alteration in Some Lupus Patients >
Research Results — Exploring Toll-Like Receptors’ (TLR) Role in Lupus >
Research Results – The Role of Myeloid Dendritic Cells in Lupus >
News Flash – American College of Rheumatology Annual Meeting Update >
FDA Warning on Rituximab >
Drug Research and Development News >
Beyond the Research - 2007 Walk Sites Announced >

Research Results - Rituximab Results in Long-Term Immune Alteration in Some Lupus Patients

One of the most anticipated new treatments for lupus is the monoclonal antibody rituximab (Rituxan), approved for use in patients with non-Hodgkin lymphoma and rheumatoid arthritis. Although the drug is already being used “off label” in some lupus patients, large clinical trials are currently underway to determine its safety and efficacy. Depending on their outcome, rituximab manufacturer Genentech plans to ask the Food and Drug Administration to approve the drug’s use in lupus patients. Even as those trials continue, researchers like ALR-funded Jennifer H. Anolik, M.D., Ph.D., at the University of Rochester Medical Center are trying to learn more about how the drug works in the body and its long-term effects on the immune system.

In an article published in September in the online version of the journal Clinical Immunology, Dr. Anolik and her team examined peripheral blood cells from 11 lymphoma patients who received rituximab. They found that when B cells returned, or were “reconstituted,” they tended to be immature, quite different from normal B cells. They also found a correlation between the degree of immaturity in reconstituted B cells and the long-term clinical response of the lymphoma patients, with higher levels of immature B cells associated with longer-term clinical responses.

“Our hypothesis is that the link is related to the degree of B cell depletion,” says Dr. Anolik. In other words, the greater the depletion of B cells during the therapy, the greater the return of immature B cells, which bodes well for any disease related to an overeager immune system. Dr. Anolik and her group also found very few “memory” B cells, the type that allow for a faster immune response during exposure to foreign antigens. “This suggests a long-term alteration to the immune system,” she said, something that could be very important to lupus patients. However, she warns, these lymphoma patients were only followed an average of a year and a half; over time, they may start to re-accumulate memory B cells.

Dr. Anolik and her group also reported on a similar investigation in lupus patients at the annual meeting of the American College of Rheumatologyin November (see related story on page 6). They followed 10 lupus patients who had taken rituximab, also finding immature peripheral blood B cell reconstitution. The B cell reconstitution was quite similar to that seen in the lymphoma patients, although with more variability.

“The reconstitution resembles what we see in a newborn’s immune system, or in patients after a bone marrow transplant,” explained Dr. Anolik, “suggesting that we can reset the immune system with this therapy, at least in some patients.” In addition, she found that like the lymphoma patients, lupus patients who experienced the longest remission had the most transitional B cells and the least memory B cells for several years after treatment.

However, the findings also suggest the need for a better understanding of infectious risks and response to vaccination in rituximabtreated patients with immature B cell reconstitution. Meanwhile, patients who don’t show significant signs of immature B cell reconstitution may require additional treatment.

Anolik JH, Friedberg JW, Zheng B, Barnard J, Owen T, Cushing E, Kelly J, Milner EC, Fisher RI, Sanz I. B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell ontogeny. Clin Immunol. 2006 Sep 26.

Just the Facts

What the study showed: Patients with lymphoma or lupus treated with rituximab show immature B cell reconstitution in their peripheral blood for a year or more after the initial treatment, and a significantly lower number of memory B cells, suggesting long-term changes in the immune system.

What it means: B cells are the primary producers of autoantibodies in lupus patients. Finding that B cell reconstitution after treatment with rituximab results in immature B cells suggests long-term suppression of the disease even after rituximab treatment ends.

What’s next: Examining B cell reconstitution in patients’ lymph nodes.

ALR funding: $75,000 – Pilot Grant funding

1.5 million

people in the U.S. have Lupus.

172 million

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