Decreased CD20 expression in rheumatoid arthritis synovium following 8 weeks of rituximab therapy

Objective. To characterise the effects of rituximab on synovial tissue of patients with refractory rheumatoid arthritis (RA). Methods. Arthroscopic biopsy of knee joint synovium was performed on 6 patients with seropositive RA prior to commencing rituximab. Four patients underwent repeat biopsy eight weeks following completion of their rituximab infusion schedule. Cryostat sections of synovium were prepared and stained with mouse monoclonal specific antibodies including CD20, plasma cell antibody and CD68. Results. Eight weeks after treatment mean DAS28 fell from 6.6 +/- 0.43 to 4.7 +/- 0.49(p=0.068). Mean CRP fell from 86.7 +/- 27 mg/L to 20.5 +/- 7 mg/L (p<0.05). Subsynovial CD20(+) B cells were demonstrated in all six patients at baseline. B cells were completely depleted in two patients at follow-up biopsy. Complete depletion was associated with excellent clinical response. No change in subsynovial B cells was seen in one patient. One patient's follow-up arthroscopy yielded inadequate tissue. A reduction was also seen in subsynovial plasma cells and CD68(+) cells after treatment. Conclusion. B cells were present in synovial tissue of all patients with refractory RA. Complete depletion of B cells was associated with an excellent clinical response. These preliminary results suggest that early depletion of synovial B cells precedes a decrease in local inflammation leading to clinical improvement.