Contributions
Abstract: P861
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: To examine systemic changes related to the evolution of acute brain lesions, we correlated the appearance of enhancing lesions on weekly MRI with (i) plasma proteome changes; (ii) number of endothelial microvesicles; and (iii) quantification of soluble markers related to inflammation and endothelial stress.
Methods: Five relapsing-remitting MS patients with no disease-modifying treatment were monitored by gadolinium-enhanced 3D T1-weighted MRI up to 7 weeks. Plasma samples obtained at each time were analyzed by multiplex immunoassay for protein biomarkers, by an optimized endothelial stress EV Array for detection of secreted microvesicles, and by UPLC-Tandem mass spectrometry; data were correlated with the number of enhancing lesions (n=212).
Results: Proteome analysis of plasma enabled quantitative information of 240 proteins at across time points. Principal component analysis clustered patients with high, medium and low number of enhancing lesions. Investigating the regulated proteins between high and low lesion patients identified clusters of regulated protein functions including negative regulators of endopeptidase activity, complement system and humoral immune response. Further correlation analysis revealed regulatory nodes in the complement system. In the patient with high number of enhancing lesions, the number of CD142- and CD51-positive EVs reflected the temporal profile of lesion evolution. Microvesicles characterized by surface markers correlated with each other and with cytokines IL-1 and IL-12p40. The number of new enhancing lesions correlated with higher levels of IL-17.
Conclusions: Evolution of enhancing lesions is accompanied by alteration of proteome, endothelial microvesicles and soluble markers of inflammation/endothelial stress in the blood.
Disclosure: Allan Stensballe: nothing to disclose, Kenneth Kastaniegaard: nothing to disclose, Malene Møller Jørgensen: nothing to disclose Rikke Bæk nothing to disclose, Tobias Sejbaek: nothing to disclose, Tue Bjerg Bennike: nothing to disclose, Christian Wiwie: nothing to disclose, Jan Baumbach: nothing to disclose, François Cotton: nothing to disclose, Charles RG Guttman: nothing to disclose, Zsolt Illes: nothing to disclose
Funding: Scleroseforeningen R367-A23541, R399-A28099, Lundbeckfonden R118-A11472, Region of Southern denmark 14/24200, Odense University Hospital A474, Agence Nationale de la Recherche ANR-10-COHO-002, PRO‐MS, the Danish National Mass Spectrometry Platform for Functional Proteomics funded by the Danish Research Agency
Abstract: P861
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: To examine systemic changes related to the evolution of acute brain lesions, we correlated the appearance of enhancing lesions on weekly MRI with (i) plasma proteome changes; (ii) number of endothelial microvesicles; and (iii) quantification of soluble markers related to inflammation and endothelial stress.
Methods: Five relapsing-remitting MS patients with no disease-modifying treatment were monitored by gadolinium-enhanced 3D T1-weighted MRI up to 7 weeks. Plasma samples obtained at each time were analyzed by multiplex immunoassay for protein biomarkers, by an optimized endothelial stress EV Array for detection of secreted microvesicles, and by UPLC-Tandem mass spectrometry; data were correlated with the number of enhancing lesions (n=212).
Results: Proteome analysis of plasma enabled quantitative information of 240 proteins at across time points. Principal component analysis clustered patients with high, medium and low number of enhancing lesions. Investigating the regulated proteins between high and low lesion patients identified clusters of regulated protein functions including negative regulators of endopeptidase activity, complement system and humoral immune response. Further correlation analysis revealed regulatory nodes in the complement system. In the patient with high number of enhancing lesions, the number of CD142- and CD51-positive EVs reflected the temporal profile of lesion evolution. Microvesicles characterized by surface markers correlated with each other and with cytokines IL-1 and IL-12p40. The number of new enhancing lesions correlated with higher levels of IL-17.
Conclusions: Evolution of enhancing lesions is accompanied by alteration of proteome, endothelial microvesicles and soluble markers of inflammation/endothelial stress in the blood.
Disclosure: Allan Stensballe: nothing to disclose, Kenneth Kastaniegaard: nothing to disclose, Malene Møller Jørgensen: nothing to disclose Rikke Bæk nothing to disclose, Tobias Sejbaek: nothing to disclose, Tue Bjerg Bennike: nothing to disclose, Christian Wiwie: nothing to disclose, Jan Baumbach: nothing to disclose, François Cotton: nothing to disclose, Charles RG Guttman: nothing to disclose, Zsolt Illes: nothing to disclose
Funding: Scleroseforeningen R367-A23541, R399-A28099, Lundbeckfonden R118-A11472, Region of Southern denmark 14/24200, Odense University Hospital A474, Agence Nationale de la Recherche ANR-10-COHO-002, PRO‐MS, the Danish National Mass Spectrometry Platform for Functional Proteomics funded by the Danish Research Agency