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Abstract Number: 991

The Alternative CD20 Transcript Variant Is Not a Factor for Resistance to Rituximab in Patients with Rheumatoid Arthritis

Cecile Gamonet1, Marina Deschamps2, Sandrine Marion3, Philippe Saas4, Gilles Chioccha3, Christophe Ferrand4 and Eric Toussirot5,6, 1INSERM UMR1098, Etablissement Français du Sang / Université de Franche Comté, Besançon, France, 2INSERM UMR1098 / Etablissement Français du Sang/ Université de Franche Comté, Besançon, France, 3Chronic Inflammation and Immune System Labex Inflamex, Université Versailles Saint Quentin, Montigny le Bretonneux, France, 4Etablisement Français du Sang ; Université de Franche Comté, INSERM UMR1098, Besançon, France, 5Clinical Investigation Centre Biotheraoy CIC 1431, Rheumatology Department, Univesity Hospital, besancon, France, 6Rheumatology, University hospital, Besançon, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: B cells, rheumatoid arthritis (RA) and rituximab

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Session Information

Session Title: B cell Biology and Targets in Autoimmune Disease: Rheumatoid Arthritis and Related Diseases

Session Type: Abstract Submissions (ACR)

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]


Disclosure:

C. Gamonet,
None;

M. Deschamps,
None;

S. Marion,
None;

P. Saas,
None;

G. Chioccha,
None;

C. Ferrand,
None;

E. Toussirot,
None.

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