title: Antiendothelial cell antibodies induce apoptosis of bone marrow endothelial progenitors in systemic sclerosis.
abstract: OBJECTIVE
  Patients with systemic sclerosis (SSc) have significantly fewer and functionally impaired endothelial progenitor cells (EPC) in peripheral blood and bone marrow; further, endothelial apoptosis seems to play a primary role in the pathogenesis of vascular damage. We investigated whether the failure of bone marrow EPC is related to their apoptotic phenotype and analyzed the possible mechanisms inducing apoptosis.
  
  
  METHODS
  The presence of apoptotic cells was investigated in bone marrow aspirates taken from patients with SSc; microvessel density (MVD) and the immunohistochemical expression of vascular endothelial growth factor (VEGF) were also measured in bone marrow biopsies. A correlation between EPC apoptosis and the presence of antiendothelial cell antibodies (AECA) was also investigated.
  
  
  RESULTS
  We confirmed the presence of bone marrow EPC dysfunction in SSc, while hematopoiesis was not impaired. Bone marrow studies showed a high percentage of apoptotic progenitors, no signs of fibrosis or an altered MVD, and an increased VEGF index. The patients' bone marrow plasma showed significant titers of AECA, and their presence correlated with that of apoptotic progenitors. These findings were further confirmed by an in vitro assay in which the apoptosis of normal progenitors was induced by the addition of AECA+ purified IgG.
  
  
  CONCLUSIONS
  Our results showed that apoptosis in patients with SSc involves the source compartment of endothelial progenitors and correlates with AECA activity. These findings support the hypothesis that AECA may play a pathogenetic role by affecting the bone marrow EPC machinery that should repair the peripheral vascular lesions.
authors: Day Hospital Reumatologia, Ospedale G. Pini, Milan, Italy. delpapa@gpini.it
authors: Nicoletta
authors: N
authors: Del Papa
authors: Nadia
authors: N
authors: Quirici
authors: Cinzia
authors: C
authors: Scavullo
authors: Umberto
authors: U
authors: Gianelli
authors: Laura
authors: L
authors: Corti
authors: Claudio
authors: C
authors: Vitali
authors: Clodoveo
authors: C
authors: Ferri
authors: Dilia
authors: D
authors: Giuggioli
authors: Andreina
authors: A
authors: Manfredi
authors: Wanda
authors: W
authors: Maglione
authors: Francesco
authors: F
authors: Onida
authors: Michele
authors: M
authors: Colaci
authors: Silvano
authors: S
authors: Bosari
authors: Giorgio
authors: G
authors: Lambertenghi Deliliers
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D001323:Autoantibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; D010455:Peptides; C087589:anti-endothelial cell antibody