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New Hope For Rheumatoid Arthritis Sufferers: B Cells As Promising New Therapeutic Targets

Date:
June 9, 2008
Source:
Wiley-Blackwell
Summary:
B cells, precursors of autoantibody-secreting cells, have emerged as promising new therapeutic targets in autoimmune diseases, including rheumatoid arthritis.
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B cells, precursors of autoantibody-secreting cells, have emerged as promising new therapeutic targets in autoimmune diseases, including rheumatoid arthritis (RA). In particular, B cell depletion with the anti-CD20 antibody rituximab seems to work for RA patients resistant to standard disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor α (TNFα) blockers. In large trials, about half of these hard-to-treat patients respond to rituximab, achieving at least a 20 percent improvement in disease activity based on the American College of Rheumatology criteria. However, in the majority of responders, the disease relapses over time. After a single treatment with rituximab, complete remission of RA symptoms for longer than a year is very rare.

With the goal of identifying reliable predictors of response or relapse to rituximab, a trio of researchers in Germany focused on the recovery response of different B cell subsets to repeated B cell depletion. Their analysis reveals the critical role of memory B cells in the compromised immune reaction of RA and the short-term gains of rituximab therapy.

Conducted by Petra Roll, M.D., and Hans-Peter Tony, M.D., at the University of Würzburg and Thomas Dörner, M.D., an affiliate of the University of Berlin, the B cell investigation began with an open-label trial of one cycle of rituximab on 17 RA patients. The participants, 14 women and 3 men, had a median age of 51 years, a median disease duration of 14 years, and a history of failure to respond to DMARD and/or anti-TNFα therapy. 16 of the patients received 2 infusions rituximab, 1,000 milligrams each, 2 weeks apart, and one patient received 4 weekly infusions of rituximab at a dose of 375 milligrams. Blood samples from all participants were obtained at baseline, on day 15, and at a 3-month followup, and analyzed for B cell repopulation.

After receiving one cycle of rituximab, 12 of the 17 patients showed a good clinical response, with significant improvement in the Disease Activity Score in 28 joints (DAS28). At the time of B cell recovery, the IgD +, CD27+ memory B cell subset was significantly larger in the nonresponder group. Within the group of 12 responders, 6 patients experienced an early relapse of RA activity, between 24 and 40 weeks after rituximab treatment. The relapsers were characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy. 11 patients were re-treated and again achieved a good clinical response. After the second cycle of rituximab, the pattern of B cell reconstitution was repeated. The number of B cells was still reduced at the time of second depletion but recovered to levels similar to those following the first cycle of therapy. This indicates an unimpaired capacity of B cell regeneration after repeated B cell depletion.

Based on statistical analysis, the researchers found a significant correlation between the size of the IgD +, CD27+ memory B cell subset during the early phase of B cell repletion and the response to anti-CD20 treatment. “Patients with lower numbers of IgD memory cells at the beginning of peripheral B cell repopulation had a much more favorable clinical response,” notes Dr. Tony. “Therefore, the extent of memory B cell repletion seems to be a key factor influencing the pathophysiology of RA.”

While revealing a potentially important target for rituximab therapy in RA, this study calls for further research into whether patients with a high level of particular memory B cells may benefit from early re-treatment or may even require higher doses of this anti-CD20 antibody.


Story Source:

The above post is reprinted from materials provided by Wiley-Blackwell. Note: Materials may be edited for content and length.


Journal Reference:

  1. Petra Roll, Thomas Dörner, and Hans-Peter Tony. Anti-CD20 Therapy in Patients With Rheumatoid Arthritis: Predictors of Response and B Cell Subset Regeneration After Repeated Treatment. Arthritis & Rheumatism, 2008; 58 (6): 1566 DOI: 10.1002/art.23473

Cite This Page:

Wiley-Blackwell. "New Hope For Rheumatoid Arthritis Sufferers: B Cells As Promising New Therapeutic Targets." ScienceDaily. ScienceDaily, 9 June 2008. <www.sciencedaily.com/releases/2008/06/080602160801.htm>.
Wiley-Blackwell. (2008, June 9). New Hope For Rheumatoid Arthritis Sufferers: B Cells As Promising New Therapeutic Targets. ScienceDaily. Retrieved July 7, 2015 from www.sciencedaily.com/releases/2008/06/080602160801.htm
Wiley-Blackwell. "New Hope For Rheumatoid Arthritis Sufferers: B Cells As Promising New Therapeutic Targets." ScienceDaily. www.sciencedaily.com/releases/2008/06/080602160801.htm (accessed July 7, 2015).

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