Burkhard Moller
Arthritis Research & Therapy 2009, 11:R62doi:10.1186/ar2686
| Published: | 6 May 2009 |
Reconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B cell stages, and their correlation to disease activity, might facilitate our understanding of innate and adaptive B cell functions in rheumatoid arthritis (RA).
35 RTX naive RA patients with active arthritis were treated after failure of tumour necrosis factor blockade in an open label study with 2 infusions of 1000 mg RTX. Prednisone dose was tapered according to clinical improvement, from median 10 mg at baseline to 5 mg at 9 months and 12 months. Conventional disease modifying antirheumatic drugs were kept stable. Subsets of CD19+ B cells were assessed by flow cytometry according to their IgD and CD27 surface expression. Their absolute number and relative frequency in PB was followed every 3 months, and was in parallel determined in synovial tissue (n=3) or synovial fluid (n=3) in the case of florid arthritis.
6 of 35 patients fulfilled the EULAR criteria for moderate, and 19 other for good, clinical response. All PB B cell fractions decreased significantly in their number (P<0.001) after 1st infusion. Disease activity developed independently of the total B cell number. B cell repopulation was dominated in quantity by CD27-IgD+ naive B cells. Low number of CD27+IgD- class-switched memory B cells (MemB) in the blood, together with sustained reduction of rheumatoid factor serum concentrations correlated with good clinical response. Class-switched MemB were found accumulated in flaring joints.
The present data support the hypothesis that control of adaptive immune processes involving germinal centre-derived, antigen and T cell dependently matured B cells is essential for successful RTX treatment.
http://arthritis-research.com/content/11/3/R62HI Lyn, forgive me but it is either too late or I am experiencing brain fog, is this good or bad news for rituxan users? I don't understand exactly what it means, thanks anyway, Janie.