Session Title: B-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: 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.
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 (< 10 mg/j) or anti TNFa agents, but none received or had received RTX. Five patients with RA requiring treatment with RTX were also evaluated prior to the first RTX infusion and during a one year follow- up study. 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. This analysis was performed on peripheral blood B cells from patients with RA and HC and synovial tissue from RA patients obtained during surgery.
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 vs211± 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.
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 response in auto-immune diseases like RA. We are currently examining whether B cell stimulation may help to evidence ΔCD20 expression in RA B-cells
1- Henry C et al., Blood, 2010;115:2420-9
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-alternative-%ce%b4cd20-transcript-variant-is-not-expressed-in-b-cells-and-synovial-tissue-from-patients-with-rheumatoid-arthritis/