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. 2009 Apr 1;6(1):13-19.
doi: 10.1016/j.ddstr.2009.10.001.

Indications of rituximab in autoimmune diseases

Iñaki Sanz  1
Affiliations

Indications of rituximab in autoimmune diseases

Iñaki Sanz. Drug Discov Today Ther Strateg. .
No abstract available

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Figures

Figure 1
Figure 1. The different phases and mechanisms of action of B cell depletion therapy
As indicated by multiple studies in different autoimmune diseases, clinical benefit may be evident shortly after the decline of peripheral B cells and before significant changes in autoantibody levels. These observations suggest that the initial benefit of this therapy is mediated at least in part by the elimination of antibody-independent pathogenic B cell functions. Chronologically, at least in some diseases, significant decreases in autoantibodies (such as dsDNA, ANCA and RF) may ensue after several weeks presumably reflecting the depletion of short-lived plasma cells secondary to the elimination of their B cell precursors and of a fraction of immature plasma cell expression some level of surface CD20. Whether chronic depletion of B cells induced by repeated courses of Rituximab will eventually result in significant declines of long-lived, CD20- plasma cells and of the autoantibodies they produce remains to be established. If so, this change (which could also potentially be achieved in combination with other agents that directly or indirectly impact plasma cell survival) could have profound consequences for the long-term course of the disease. In any case, animal experiments as well as observations in a subset of SLE patients with long-term remissions after BCDT strongly suggest that in at least some diseases or disease subsets, the delayed but critical benefit of rituximab might be the promotion of expansion of B cells with protective functions that might include the induction of T cell anergy, promotion of Treg cells and the production of regulatory cytokines. While for illustration purposes this figure assigns pathogenic and regulatory functions to memory and transitional/naïve cells respectively, the actual division of labor between B cell subsets remains to be elucidated and is likely to be significantly more complex than depicted here.
See this image and copyright information in PMC

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