title: Serum levels of vascular dysfunction markers reflect disease severity and stage in systemic sclerosis patients.
abstract: To improve knowledge of vasculopathy in SSc through the assessment of serum levels of circulating angiogenetic and endothelial dysfunction markers in patients at different stages of the disease.
  
  
  
  Sera from 224 subjects were obtained and concentrations of angiopoietin-2, chemokine (C-X-C motif) ligand (CXCL)-16 (CXCL16), E-selectin, soluble intercellular adhesion molecule-1, IL-8 (CXCL8), soluble vascular adhesion molecule-1 and VEGF were determined by a Luminex assay. Subjects included 43 healthy controls, 47 early SSc patients according to LeRoy and Medsger without other signs and symptoms of evolutive disease, 48 definitive SSc (defSSc) patients according to the 2013 ACR/EULAR criteria without skin or lung fibrosis, 51 lcSSc subjects and 35 dcSSc subjects.
  
  
  
  The four groups of patients showed well-distinct clinical and laboratory characteristics, with a linear decreasing trend in forced vital capacity and diffusing capacity for carbon monoxide % predicted values from early SSc to defSSc to lcSSc and to dcSSc, and a linear increasing trend in ESR, and in the prevalence of abnormal CRP, serum gamma globulins and lung fibrosis (all P < 0.0001). Highly significant linear trends pointing to an increase in angiopoietin-2 (P < 0.0001), CXCL16 (P < 0.0001), E-selectin (P = 0.001) and soluble intercellular adhesion molecule-1 (P = 0.002) in relation to the different disease subsets were observed.
  
  
  
  Markers characterizing vascular activation are found to be increased in SSc patients from the earliest stages of disease when clinical and laboratory findings of advanced disease cannot yet be detected. These abnormalities progress with the appraisal of the first sclerodermatous manifestation in defSSc and further increase with the onset of fibrotic manifestations.
authors.affiliation: Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center, Utrecht, Netherlands and.
authors.forename: Marta
authors.initials: M
authors.lastname: Cossu
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Andracco
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santaniello
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marchini
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Severino
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Caronni
authors.affiliation: Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center, Utrecht, Netherlands and.
authors.forename: Timothy
authors.initials: T
authors.lastname: Radstake
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Referral Center for Systemic Autoimmune Diseases, Milano, Italy lorberimm@hotmail.com.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
mesh_terms: D000328:Adult; D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood; D020533:Angiogenesis Inhibitors / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000097:blood; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D051116:Receptors, Scavenger / Q000097:blood; D012595:Scleroderma, Systemic / Q000097:blood* / Q000503:physiopathology; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D015415:Biomarkers; C423727:CXCL16 protein, human; D015815:Cell Adhesion Molecules; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D019040:E-Selectin; D018836:Inflammation Mediators; D016209:Interleukin-8; D051116:Receptors, Scavenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)
keywords: adhesion molecules; angiogenesis; early disease; systemic sclerosis