THU0043 The Alternative CD20 Transcript Variant is not Expressed in B Cells and Synovial Tissue from Patients with Rheumatoid Arthritis

2013 
Background determining predictive factors for response to biologics may help to select appropriate treatment in patients with RA. Rituximab (RTX) is a chimeric monoclonal antibody directed against the membrane CD20 protein present on B cells. Predictive factors for good response to RTX therapy in RA have been identified and included the presence of rheumatoid factors and anti -CCP antibodies. A spliced mRNA transcript of CD20 (ΔCD20) has been observed in B cell lines from patients with lymphoma and leukaemia (1). This transcript is coding for a non anchored membrane protein and its expression is associated with resistance to RTX in patients with haematological malignancies. Objectives to determine whether ΔCD20 is expressed by circulating B cells and synovial tissue from patients with RA and whether it could be a factor for non response to RTX therapy in RA. Methods 23 RA patients (17 F, age (mean ± SEM): 60.1 ± 2.7 years; disease duration: 13.3 ± 1.7 years, positive rheumatoid factors: 19/23; positive anti- CCP antibodies: 19/23) and 20 healthy controls (HC) (15 F, age: 59.6 ± 2.5 years) were evaluated. Patients were under DMARDs, low corticosteroids ( Results RA patients had mild active disease (DAS28 score: 3.3 ± 0.3; CRP levels: 6.8 ± 1.9 mg/l). Number of circulating B cells per µl was not different between RA patients and controls (mean ± SEM, range: 184± 22, 18-437 vs 211± 27, 63-408, respectively). Among all the 23 RA samples, although full length CD20 expression was always detected, we were unable to detect ΔCD20, even with the more sensitive RT-PCR assay permitting to identify the spliced transcript form. Among the 5 patients who received RTX, 4 well responded to the treatment. -Both responders and non responder patients did not express ΔCD20 before RTX administration and during the follow-up study. ΔCD20 was also not detected in synovial tissue samples from 5 patients with RA. Conclusions The present study showed that, on the contrary of leukemic or lymphoma B cells, RA B-cells and synovial tissue from RA patients do not express ΔCD20, suggesting that this transcript may be a molecular marker of malignancies rather than a factor predictive to RTX responses in auto-immune diseases like RA. We are currently examining whether B cell stimulation may help to evidence ΔCD20 expression in RA B-cells References Henry C et al ., Blood, 2010;115:2420-9 Disclosure of Interest None Declared
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