Update: B-Cells in Rheumatic Disease
Volume 1 | January 1, 2006 – March 31, 2006
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Highest Rated Articles
In this open-label study of 15 RA patients, Rituximab infusions were shown to induce a mean >97% loss of circulating B-lineage cells and decreases in RF and anti-CCP antibodies, which was associated with early reciprocal increases in serum BAFF/BLyS, a potent B-cell survival factor. BAFF increases generally persisted as long as blood B-cell levels remained depleted, but with return of blood B cells median BAFF/BLyS levels were significantly higher in pts with more prolonged clinical responses compared to patients in whom B-cell return was closely associated with clinical relapse. These studies suggested an interdependence between BAFF levels and B-cell regeneration, and potential effects on the expansion of disease-associated memory B cells that have infiltrated affected rheumatoid synovial sites.
In this open-label study of 24 RA patients, after Rituximab induced blood B-cell depletion most remaining B cells were shown to be memory B cells and plasma cells. The later recovery period was primarily due to increases in naïve immature B cells believed to newly arise in the bone marrow. In many RA patients, levels of circulating memory B cells were slow to recover after treatment; while patients who displayed higher post-treatment levels of CD27+ memory B cells during recovery more often had early clinical relapses. These studies suggest that clinical benefits from anti-CD20 therapy may reflect induced shifts in B-cell compartments with reductions in memory B cell, which presumably include autoreactive B cells involved in immunopathogenesis.
In this trial of 36 pediatric (2.6 to 18.3 yrs) patients with chronic treatment-resistant ITP represents the only such prospective rituximab trial to date. All 33 patients who completed all infusions displayed profound induced blood B-cell depletions, and 31% achieved the primary endpoint of sustained platelet count of > 50,000/mm3, with a median response time of 1 week. While IgG levels were little affected, subnormal IgM levels were common but not associated with increased incidence of infection. While treatments were generally well tolerated, 6% of pts developed serum sickness, an incidence much higher than reported for lymphoma treatment.
Moreland L. Unmet needs in rheumatoid arthritis. Arthritis Research & Therapy. 2005; 7 Suppl 3:S2-8.
A leader in RA clinical trial investigation provides a thorough overview of the most recent controlled trials, and the state of the art regarding DMARDs, biologic agents and combination regimens, differences in study populations, outcomes and clinical responses. Issues with regard to heterogeneity in clinical responsiveness, and known and emerging safety issues are identified and succinctly discussed.
