Understand Pathogenicity of SSc-specific Antibodies in SSc and the Effect of Antibody Blockade in Vitro
Conditions
Brief summary
Established in vitro assays, combined with state-of-the-art multi-omics approaches and innovative in vitro experimental models, will gain insights into the mechanistic bases underlying Systemic Sclerosis (SS) pathogenesis and will dissect the consequences of treatment with Efgartigimod on functional and phenotypic cell behaviors. Healthy microvascular endothelial cells, fibroblasts and monocytes will be challenged with serum and autoantibodies prior to or upon treatment with Efgartigimod in order to assess both the prevention and the recovery capacity of the FcR blocker. The putative modulatory effect of Efgartigimod on vascular remodeling, endothelial-to-mesenchymal transition, fibroblast-to-myofibroblasts transition and monocyte behavior will be evaluated in in-vitro consolidated assays. Integrated Omics analyses will support and complement the in vitro findings by unveiling potential prognostic signatures and by identifying specific treatment-related profiles that might guide the modulation of the drug usage in order to maximize its beneficial effects.
Interventions
BIOLOGICALFcr blocker of autoantibodies
in vitro assays, combined with multi-omics approach and in vitro experimental models, will gain insights into the pathogenesis of Systemic Sclerosis (SSc)dissecting the consequences of treatment with Fcblocker on functional and phenotypic cell behavior. Healthy microvascular endothelial cells, fibroblasts and monocytes will be challenged with serum and autoantibodies prior to or upon treatment with Efgartigimod in order to assess both the prevention and the recovery capacity of the FcR blocker. The putative modulatory effect of Efgartigimod on vascular remodeling, endothelial-to-mesenchymal transition, fibroblast-to-myofibroblasts transition and monocyte behavior will be evaluated in in-vitro consolidated assays. Integrated Omics analyses will support and complement the in vitro findings by unveiling potential prognostic signatures and by identifying specific treatment-related profiles that might guide the modulation of the drug usage in order to maximize its beneficial effect
Sponsors
IRCCS Ospedale San Raffaele
Study design
Observational model
CASE_ONLY
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* positivity of autoantibodies
Exclusion criteria
* pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Verify if Fcblocker can block the pathogenic activity of autoantibodies | 24 months | To assess both the prevention and the recovery capacity of the FcR blocker in different kind of cells submitted to the specific autoantibody. microvascular endothelial cells and fibroblasts |
Contacts
Primary ContactmARCO matucci cerinic, MD PHD
Outcome results
None listed