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B cells: depletion or functional modulation in rheumatic diseases.

Thomas Dörner1, Peter E Lipsky

  • 1aDepartment of Rheumatology and Clinical Immunology, CC12 Department of Medicine, Deutsches Rheuma-Forschungszentrum Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany bNIAMS, NIH, Bethesda, Maryland, USA.

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B-cell-targeting therapies are revolutionizing rheumatic autoimmune/inflammatory diseases (RAIDs) treatment. Further research is needed to distinguish the efficacy and safety of B-cell depletion versus modulation for specific RAIDs.

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Area of Science:

  • Immunology
  • Rheumatology
  • Pharmacology

Background:

  • B lymphocytes play a critical role in rheumatic autoimmune/inflammatory diseases (RAIDs).
  • Recent advancements in B-cell-targeted therapies have renewed focus on their therapeutic potential in RAIDs.
  • The distinct therapeutic roles of B-cell modulation in specific RAIDs require further investigation.

Purpose of the Study:

  • To review the current landscape of B-cell-targeting drugs for RAIDs.
  • To assess the distinct therapeutic potential of these agents in various RAIDs.
  • To highlight translational advances and future research directions.

Main Methods:

  • Review of recent studies on B-cell-directed drugs and their effects on RAIDs.
  • Analysis of clinical development of novel agents targeting B-cell surface molecules and cytokines.
  • Evaluation of insights into protective immunity and RAID mechanisms influenced by current therapies.

Main Results:

  • Several drugs targeting B-cell surface molecules (e.g., CD19, CD20) and cytokines (e.g., IL-6, BAFF) are in clinical development.
  • Existing therapies like rituximab and belimumab show effects on protective immunity and RAID progression.
  • The impact of B-cell-directed drugs on immune activation and chronic maintenance may vary across different RAIDs.

Conclusions:

  • Translational advances focus on B-cell depletion and modulating B-cell functions, including B-cell receptor signaling and memory B/plasma cell survival.
  • Further delineation of efficacy and safety profiles is crucial for B-cell depletion versus B-cell modulation strategies.
  • Antigen-specific tolerance induction represents a promising avenue for B-cell modulation.