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Abstract Number: 2103

Peripheral Blood B Cells Are Expanded and Their Cytokine Expression Is Dysregulated in Juvenile Dermatomyositis

Meredyth Wilkinson1, Christopher Piper2, Georg Otto3, Claire Deakin4, Stefanie Dowle3, Stefania Simou5, Daniel Kelberman3, Yiannis Ioannou6, Claudia Mauri7, Elizabeth Jury8, David Isenberg9, Lucy R Wedderburn10 and Kiran Nistala11, 1Division of Medicine, University College London, London, United Kingdom, 2Rheumatology, University College London, London, United Kingdom, 3National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom, 4Infection, Inflammation and Rheumatology Section,, UCL Institute of Child Health, London, United Kingdom, 5Infection, Inflammation and Rheumatology, UCL Institute of Child Health, London, United Kingdom, 6Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom, 7Division of Medicine, Centre for Rheumatology Research, University College London, University College London, London, United Kingdom, 8Division of Medicine, Centre for Rheumatology Research, University College London, London, United Kingdom, 9University College Hospital, London, London, United Kingdom, 10Infection, Inflammation and Rheumatology Section, UCL Institute of Child Health, London, United Kingdom, 11Centre for Rheumatology, University College London, London, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: B cells, cytokines, dermatomyositis, interferons and juvenile dermatomyositis

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Session Information

Date: Tuesday, November 15, 2016

Session Title: B Cell Biology and Targets in Autoimmune Disease - Poster II: Rheumatoid Arthritis and Other Rheumatic Diseases

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and heliotrope rash. B cells are strongly implicated in the pathogenesis of the disease and can generate myositis specific antibodies, that are associated with clinical subgroups. We propose that B cells may also contribute to the disease by producing pro-inflammatory cytokines, triggered by type I interferons.

Methods: Samples and data were collected from children with JDM recruited to the UK JDM Cohort and Biomarker Study. Peripheral blood mononuclear cells (PBMC) samples from JDM patients before treatment and on treatment were selected for analysis. PBMC from child healthy controls (CHC) (n=25) and JDM patients (n=61) were incubated in the presence of phorbol 12-myristate 13-acetate (PMA), Ionomycin and Golgi Plug for 4hrs and cytokine expression was analysed by flow cytometry. PBMC and sorted B cells were also stimulated for 48hr with R848 (TLR7/8) and assessed for intracellular IL-6 and IL-10 by flow cytometry and protein levels were measured by ELISA. PBMC were stained ex-vivo to look at B cell subset frequency and Ki67 expression. Differences between groups were analysed using paired/unpaired t tests or one-way ANOVA (Prism 6 software). 

Results: B cell frequency was significantly higher in pre-treatment JDM patients compared to CHC samples (mean frequency of total PBMC 25.72% Vs. 22.69% (ns) (£6 months treatment) or 16.26% in CHC; p<0.01). This difference was most marked in the immature B cell subset (mean frequency of total B cells 36.05% Vs. 3.66% (£6 months on treatment) or 12.4% in CHC; p<0.01). The immature B cell subset was more proliferative before treatment (mean Ki-67% of 17.63% Vs. 8.86% (>6 months on treatment) or 7.18% in CHC; p<0.01). Whole transcriptome RNA sequencing of B cells from paired pre and on treatment patient samples showed an upregulation of the type I interferon signature. Of particular interest Toll-like receptor 7 (TLR7) was up-regulated in B cells from patients’ pre-treatment. When B cells were stimulated with TLR7 agonist (R848) there was reduced expression of IL-10 detected by ELISA from JDM compared to CHC samples (10.61pg/ml Vs. 75.01pg/ml (mean values)). However, IL-6 expression responded the same in JDM compared to CHC (486.18pg/ml Vs. 414.29pg/ml (mean values)).

Conclusion: We have identified a subset of immature B cells that are expanded, more proliferative and express both IL-6 and IL-10 in pre-treatment patients. The up-regulated type I interferon signature in JDM could contribute to the expansion of immature B cells with an imbalance of IL-6 and IL-10 production.


Disclosure: M. Wilkinson, None; C. Piper, None; G. Otto, None; C. Deakin, None; S. Dowle, None; S. Simou, None; D. Kelberman, None; Y. Ioannou, None; C. Mauri, None; E. Jury, None; D. Isenberg, None; L. R. Wedderburn, None; K. Nistala, None.

To cite this abstract in AMA style:

Wilkinson M, Piper C, Otto G, Deakin C, Dowle S, Simou S, Kelberman D, Ioannou Y, Mauri C, Jury E, Isenberg D, Wedderburn LR, Nistala K. Peripheral Blood B Cells Are Expanded and Their Cytokine Expression Is Dysregulated in Juvenile Dermatomyositis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/peripheral-blood-b-cells-are-expanded-and-their-cytokine-expression-is-dysregulated-in-juvenile-dermatomyositis/. Accessed December 5, 2019.
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