Abstract | OBJECTIVE: B cell depletion with the anti-CD20 antibody rituximab has proven efficacy in patients with rheumatoid arthritis (RA). The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known. METHODS: In this open-label study, 17 patients with RA refractory to standard therapy were treated with 1 cycle of rituximab. Of these 17 patients, 11 received a second cycle of rituximab therapy. Immunophenotyping was performed before therapy and during B cell recovery. RESULTS: Twelve of 17 patients showed a good European League Against Rheumatism response after receiving 1 cycle of rituximab therapy. At the time of B cell recovery, the IgD+,CD27+ memory B cell subset was significantly larger (P = 0.019) in the nonresponder group. Within the group of 12 responders, 6 patients, whose disease was characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy, experienced an early relapse (weeks 24-40 posttreatment). Eleven patients were re-treated, again resulting in a good clinical response. B cell reconstitution followed a similar pattern after each cycle. The early reconstitution phase was characterized by immature CD38++, IgD+,CD10+ B cells, whereas the number of naive B cells increased continuously thereafter. The number of memory B cells was still reduced at the time of the second depletion but recovered to levels similar to those following the first cycle of therapy. CONCLUSION: Data derived from repeated B lymphocyte depletion with rituximab in patients with RA suggest that analysis of certain memory B cell subsets provides information on efficacy, response, and late as well as early relapse, consistent with the conclusion that targeting memory B cells is a key to its mechanism of action.
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Authors | Petra Roll, Thomas Dörner, Hans-Peter Tony |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 58
Issue 6
Pg. 1566-75
(Jun 2008)
ISSN: 0004-3591 [Print] United States |
PMID | 18512772
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD20
- Biomarkers
- Immunoglobulin D
- Immunologic Factors
- Rituximab
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD20
(immunology)
- Arthritis, Rheumatoid
(drug therapy, immunology)
- B-Lymphocyte Subsets
(classification, drug effects)
- Biomarkers
(blood)
- Female
- Humans
- Immunoglobulin D
(drug effects)
- Immunologic Factors
(therapeutic use)
- Male
- Middle Aged
- Recurrence
- Remission Induction
- Rituximab
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