Background Targeting B cells is an effective therapy in rheumatoid arthritis (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. Recently, a spliced mRNA transcript of CD20 (ΔCD20) has been identified in B cell lines from patients with lymphoma and leukaemia (ref.). 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 from patients with RA and whether it could be a factor for non response to RTX therapy.
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 (15 F, age: 59.6±2.5 years) were evaluated. Patients were under DMARDs, low corticosteroids (<10 mg/j) or anti TNFa agents but none received or had received RTX. CD20 mRNA expression study was performed using RT-PCR assay allowing first to discriminate full length CD20 (membrane CD20) from ΔCD20 transcripts. A more sensitive RT-PCR assay, using a specific primer spanning the splice fusion area was then used to detect specifically only the ΔCD20 transcript.
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.
Conclusions The present study showed that, on the contrary of leukemic or lymphoma B cells, RA B-cells do not express ΔCD20, suggesting that this transcript may be a molecular marker of malignancies rather than of auto-immune diseases like RA. Study of RTX-non responders or -escaping RA patients may be relevant to know if ΔCD20 expression may be detected under the pressure of RTX therapy.
Henry C et al., Blood, 2010;115:2420-9
Disclosure of Interest None Declared
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