Session Information
Date: Sunday, November 8, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
CD19 is a membrane glycoprotein of the immunoglobulin superfamily and part of the hetero-oligomeric complex comprising the complement receptor type 2, which positively regulates BCR activation. In the tight skin (TSK/+) mouse model for human SSc it has been demonstrated that down regulation of CD19 significantly decreased skin fibrosis, B cell hyper proliferation and IL-6 production.
The purpose of this study was to analyze the effect of rituximab treatment (RTX) in rheumatoid arthritis (RA) and systemic sclerosis (SSc) patients on the CD19-expression on peripheral blood B cells.
Methods: B cells from 21 RA patients and 8 SSC patients were analyzed before and 24 or 48 weeks after initiation of the B cell depleting therapy with RTX. RA patients received 2x 1000mg RTX and the DAS28 was determined before and 24 months thereafter to calculate the EULAR response. SSc patients received 2x 500mg RTX every 3 month and the Rodnan skin score (RSS) and the diffusing capacity of the lung for carbon monoxide (DLCO) were measured before and 48weeks later. CD19 surface expression was determined by mean fluorescence intensity (MFI) and compared with the MFI of CD45 on the cells of interest. B cells were divided into naïve (IgD+/CD27-) and post switch memory cells ((IgD-/CD27+).
Results: Fifteen RA patients had after 6 month a good EULAR response, whereas 6 RA patients were EULAR non responders. In contrast, all SSc patient had a significant improvement in their RSS and DLCO after 1 year. The MFI of CD45 on B cells was not significantly different from the MFI on non B cells and was similar between the patients group. Thus, the MFI±SEM on B cells of RA and SSC patients before RTX was 40,890 ± 2,240 and 32,129 ± 6,718, respectively. The respective CD45 MFI on non-B cells was 41,123 ± 2,896 and 35,710 ± 7,989. Even after RTX no significant alteration was found. In contrast, the MFI of CD19 was significantly reduced on B cells after RTX with the greatest reduction in SSC B cells (9,016 ± 845 and 3,804 ± 281, p≤0.0001), followed by B cells from RTX-responders (9,156 ± 719 and 5,975 ± 585, p≤0.008) and RTX-non responders (9,492 ± 603 and 6,712 ± 818, p≤0.031). Interestingly, analyzing CD19 expression on the B cell subsets demonstrated that naïve B cells in RTX-non responders had no significant reduction in MFI (9,596 ± 677 and 6,890 ± 1,302, p=0.1663) compared to RTX responders in RA ( 9,214 ± 745 and 6,466 ± 635, p≤0.018) or SSc (8,672 ± 977 and 3,673 ± 607, p≤0.016). RTX induced the down regulation of CD19 on all post switch B cells irrespective of the treatment response.
Conclusion: These data suggest, that RTX affects disease activity not only by eliminating B cells but also by reduceing the expression of the costimulatory surface molecule CD19. Interestingly, in RTX-non responders newly produced naïve B cells do not significantly down regulate CD19. Thus, they might still be able to activate T cells or produce pro inflammatory cytokines.
To cite this abstract in AMA style:
Brezinschek HP, Fürst-Moazedi F, Kielhauser S, Stradner M, Graninger W. Rituximab Non Responders Fail to Down Regulated CD19 on Naive B Cells [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/rituximab-non-responders-fail-to-down-regulated-cd19-on-naive-b-cells/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-non-responders-fail-to-down-regulated-cd19-on-naive-b-cells/