Background/Purpose: the identification of predictive factors for the response, or alternatively factors for resistance to biological agents is a relevant goal in the management of patients with rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the membrane CD20 protein expressed by B cells. Predictive factors for good response to RTX therapy in RA have been previously determined, and included presence of rheumatoid factors and anti -CCP antibodies. A spliced mRNA transcript of CD20 (D393-CD20) has been observed in tumoral B cells from patients with lymphoma and leukaemia (1). This transcript is coding for a non-anchored membrane protein and its expression may be associated with resistance to RTX in patients with haematological malignancies.

Objectives: we previously reported that this alternative D393-CD20 transcript is not expressed in B cells and synovial tissue from patients with RA. In this study, we aim to determine whether D393-CD20 is expressed by circulating B cells from patients with RA who are refractory to RTX and whether it could be a factor for non-response to this treatment. 

Methods: selected patients were from the SMART study (2). We included those who did not respond to RTX treatment (EULAR response). 24 RA patients (21 F, age [mean ± SD]: 57.6 ± 11.2 years; disease duration: 8.7 ± 6.7 years, positive rheumatoid factors: 13/24; positive anti- CCP antibodies: 13/24) were evaluated. All the patients had concomitant MTX and low corticosteroids (< 10 mg/j; 21/24). CD20 mRNA expression study was performed using RT-PCR assay allowing to discriminate full length CD20 (membrane CD20) from D393-CD20 transcripts. A more sensitive RT-PCR assay, using a specific primer spanning the splice fusion area was then used to detect specifically only the D393-CD20 transcript. This analysis was performed on peripheral blood B cells from patients with RA.

Results: RA patients had high disease activity at baseline (DAS28: 5.8 ± 0.8). Disease activity remained elevated after one course of RTX 1000 mg x 2 (DAS 28 at week 24: 5.5 ± 0.8). Among all the 24 RA samples, although full length CD20 expression was always detected, we were unable to detect D393-CD20, even with the more sensitive RT-PCR assay permitting to identify the spliced transcript form. We did not identify a subgroup of patients who display positive D393-CD20.

Conclusion: the present study showed that, on the contrary of leukemic or lymphoma B cells, RA B-cells from RA patients who did not respond to RTX do not express D393-CD20. This result, together with our previous data (lack of expression of this alternative transcript in cross-sectional analysis of RTX-naïve RA patients and in synovial tissue from RA patients) indicate that D393-CD20 may only be a molecular marker of malignancies rather than a factor predictive to RTX responses in auto-immune diseases like RA.

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

2-     Mariette X, Ann Rheum Dis, 2013 May 30 [Epub ahead of print]

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-alternative-cd20-transcript-variant-is-not-a-factor-for-resistance-to-rituximab-in-patients-with-rheumatoid-arthritis/