B Cell Differentiation Model for Identifying Predictors of Responses to Rituximab‐Mediated B Cell Depletion in Rheumatic Diseases Article Swipe
Tomohisa Nakada
,
Donald E Mager
,
Tomohisa Nakada
,
Donald E Mager
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/psp4.70151
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/psp4.70151
Rituximab (RTX), an anti‐CD20 monoclonal antibody, has been used to treat autoimmune diseases such as rheumatoid arthritis (RA). However, variability in therapeutic response to RTX remains a challenge. Here, a systems model is developed to mimic B cell differentiation leading to antibody‐secreting cells (ASCs), including plasmablasts (PBs) and plasma cells (PCs). The model features the localization of B cell subsets in the bone marrow and secondary lymphoid organs and incorporates the internalization process of the CD20–RTX complex. To reproduce clinical data from patients with RA receiving RTX and glucocorticoids, pharmacokinetic models for the drugs were built and respective pharmacodynamic profiles of CD19 + and CD20 + cells and PBs were well captured by optimizing model parameters, which were estimated with good precision. As ASCs are the primary source of pathogenic autoantibodies in RA, the extent and duration of ASC depletion were hypothesized as drivers of therapeutic response to RTX. Global sensitivity analyses identified the CD20–RTX binding affinity and elimination rate constant (i.e., Fcγ‐mediated degradation, internalization) as major determinants of both CD19 + cells and ASCs. The influence of baseline PBs and PCs on ASCs was also suggested, providing potential mechanisms underlying responder and non‐responder variability. The model accurately reproduced the temporal changes in CD19 + cells after combination treatment with RTX and glucocorticoids suggesting successful model validation. This study provides a mechanistic framework and insights into key drivers of responses to CD20‐depletion treatment using B cell dynamics as an indirect biomarker of clinical endpoints, which might ultimately improve therapeutic outcomes.
Related Topics
Concepts
CD19
B cell
Rituximab
Rheumatoid arthritis
Immunology
Autoantibody
Medicine
Bone marrow
CD20
Autoimmunity
Plasma cell
Biomarker
Monoclonal antibody
Antibody
Arthritis
Monoclonal
Cell
Cancer research
Internalization
Cellular differentiation
Immunophenotyping
Mesenchymal stem cell
Cell therapy
Biology
T cell
Autoimmune disease
Haematopoiesis
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/psp4.70151
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/psp4.70151
- OA Status
- gold
- References
- 39
- OpenAlex ID
- https://openalex.org/W7106546276
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7106546276Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/psp4.70151Digital Object Identifier
- Title
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B Cell Differentiation Model for Identifying Predictors of Responses to Rituximab‐Mediated B Cell Depletion in Rheumatic DiseasesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-11-25Full publication date if available
- Authors
-
Tomohisa Nakada, Donald E Mager, Tomohisa Nakada, Donald E MagerList of authors in order
- Landing page
-
https://doi.org/10.1002/psp4.70151Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/psp4.70151Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/psp4.70151Direct OA link when available
- Concepts
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CD19, B cell, Rituximab, Rheumatoid arthritis, Immunology, Autoantibody, Medicine, Bone marrow, CD20, Autoimmunity, Plasma cell, Biomarker, Monoclonal antibody, Antibody, Arthritis, Monoclonal, Cell, Cancer research, Internalization, Cellular differentiation, Immunophenotyping, Mesenchymal stem cell, Cell therapy, Biology, T cell, Autoimmune disease, HaematopoiesisTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
39Number of works referenced by this work
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