MD Biosciences Blog

Efficacy of anti-CD20 Therapy in Rhuematoid Arthritis

Posted by MD Biosciences

on May 11, 2010 11:46:00 AM

We read an interesting article published this week in Journal of Immunology (v184 Bottaro & co.) on the efficacy of anti-CD20 therapy in RA. The article highlights the continuing uncertaintity over the mode of action of B-cell directed therapy in Rheumatoid Arthritis (RA) [review of the differing theories is presented in Clin Exp Immunol. 2009 Aug;157(2):191-7].

Therapies such as rituximab (anti-CD20) may be involved in one or more of the following:

  • remove plasma cell precursors thereby decreasing auto-reactive monoclonal antibodies
  • deplete the B cells that act as antigen presenting cells to auto-reactive T cells
  • remove a cytokine producing B-cell population
  • disrupt peripheral lymphoid tissue
  • or a combination of the above.


The authors previously used MRI to measure the synovial volume in the TNF-Tg mice and demonstrated a relationship to popliteal lymph node (PLN) volume. They observed that synovial volume is relatively constant while PLN volume increases however when the PLN "collapses" then synovial volume increases dramatically. This lead to the question of what happens when the PLN collapses that it appears to induce the pathological synovial changes.

In this paper the authors show, by immunohistochemistry, huge changes in the PLN architecture after collapse, characterised by influx of B cells into the paracortical sinuses and T cell area. The authors characterise these B cells as a unique population of previously undefined B cells which are also present in the KBxN mouse model of RA. The authors then to go on to show that this population of B cells are depleted by anti-CD20 therapy which is also surprisingly efficacious in the TNF-Tg model despite its previous appearance of being T and B cell independent model. The overall message from the paper is definition of a unique B cell population that may be the target of anti-CD20 therapy.

 

Pre-clinical efficacy models of Rheumatoid Arthritis:

Collagen-induced arthritis
Collagen-antibody induced arthritis
Adjuvant-induced arthritis

 

Download the Whitepaper:
Collagen-antibody induced arthritis: A short, synchronized and rapid alternative to the Collagen-induced arthritis model.

collagen-antibody induced arthritis. MD Biosciences pre-clinical contract research (CRO)

Topics: Inflammation