Transcript of Scleroderma Horizon Scanning
- 1. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR
LMBRU Francesco Del Galdo MD,PhD Associate Professor/Honorary
Consultant Head of Scleroderma Programme, LMBRU Leeds Institute of
Rheumatic and Musculoskeletal Medicine University of Leeds Horizon
Scanning
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LMBRU What can we see Where do we really want to go? What do we
need to get there
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LMBRU What can we see ?
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LMBRU Systemic Sclerosis AUTOIMMUNE ACTIVATION TISSUE FIBROSIS
Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth
muscle cells
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LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY
Endothelial cells Smooth muscle cells AUTOIMMUNE ACTIVATION B
cells, T cells, Macrophages, Eosinophils
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LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY
Endothelial cells Smooth muscle cells TISSUE FIBROSIS
Fibroblasts
- 7. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR
LMBRU Systemic Sclerosis SMALL VESSEL VASCULOPATHY Endothelial
cells Smooth muscle cells
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LMBRU SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle
cells Systemic Sclerosis TISSUE FIBROSIS Fibroblasts AUTOIMMUNE
ACTIVATION B cells, T cells, Macrophages, Eosinophils TISSUE
FIBROSIS Fibroblasts
- 9. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR
LMBRU Where do we really want to go?
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LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL
VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells
AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages,
Eosinophils
- 11. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR
LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL
VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells
AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages,
Eosinophils
- 12. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR
LMBRU Reverse Translational approach Bed side to Bench Fibrotic
phenotype Multiple mechanisms confounded Extreme clinical phenotype
Identification of principal pathogenetic mechanism or marker
Integration within general cohort
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LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL
VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells
AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages,
Eosinophils
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LMBRU What do we need to get there
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LMBRU Measure Scleroderma activity and severity 1) 1) Fibrotic
process is systemic 2) 2) target organ function is affected 3) not
only by fibrotic process 4) 3) Clinical signs of organ involvement
5) emerge at different time during 6) the disease course LUNG Heart
GI
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LMBRU SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle
cells Measure Scleroderma activity and severity: Vasculopathy
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LMBRU Ann Rheum Dis 2010;69:10921096. Rheumatology 2012;51:749755
VIDEOCAPILLAROSCOPY Measure Scleroderma activity and severity:
Vasculopathy
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LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY
Endothelial cells Smooth muscle cells TISSUE FIBROSIS Fibroblasts
Abignano, 2013 Measure Scleroderma activity and severity:
Fibrosis
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LMBRU * P Clements, Rheuamtology 26% SE Measure Scleroderma
activity and severity: Skin fibrosis
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LMBRU Virtual skin biopsy by Optical Coherence Tomography: the
first quantitative imaging biomarker for scleroderma OCT ARD, 2013
Nature Review Rheumatology, 2013 Measure Scleroderma activity and
severity: Skin Fibrosis
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LMBRU Abignano, 2013 ED PD RD K * * * * DEJ HealthySSc MRSS = 3 * *
Virtual skin biopsy by Optical Coherence Tomography Skin fibrosis
by OCT
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LMBRU
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LMBRU
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LMBRU Diagnostic Evidence Cooperative
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LMBRU Combined index of progression 60m SSc sRP Full clinical +
ECHO + PFT + HRCT+ Capillaroscopy Serum biomarkers PIINP + TIMP +
NT-BNP + OCT
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LMBRU
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LMBRU OCT as biomarker of skin involvement ELF serum test as
surrogate outcome measure of fibrogenesis HO-1 as TGF-b induced
mechanism of vasculopathy SFRP4 and non canonical WNT activation in
SSc skin PEDF and melanocytes contribution to SSC vasculopathy
VEDOSS HGLA shared epitope Local care in DU Healing and rate of
infection VC of calcinosis Calsite study M. Buch Scleroderma
Research Programme G. Abignano J Ellez-Gomez J. Gillespie V.
Liakouli S Eng Research Nurse L. Loughrey B. Alcacher-Pitarch A.
Redmond J Blagojevic Caveolin in modulation of Shh pathay in
myofibroblasts K Kampsioras G. Lettieri Radiologist. Exploring MRI
and ShearWave US to predict progression of SSc hand