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THU0104 No expression of an alternative CD20 transcript variant in B cells from patients with rheumatoid arthritis
  1. M. Deschamps1,
  2. B. Gaugler1,
  3. P. Saas1,
  4. C. Ferrand1,
  5. E. Toussirot2,3
  6. and CIC Biotherapy 506
  1. 1INSERM UMR645, EFS Bourgogne Franche Comté
  2. 2CIC Biotherapy 506
  3. 3Rheumatology, University Hospital, Besançon, France

Abstract

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.

  1. Henry C et al., Blood, 2010;115:2420-9

Disclosure of Interest None Declared

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