RT Journal Article
SR Electronic
T1 Antiendothelial Cell Antibodies Induce Apoptosis of Bone Marrow Endothelial Progenitors in Systemic Sclerosis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 2053
OP 2063
DO 10.3899/jrheum.091346
VO 37
IS 10
A1 NICOLETTA DEL PAPA
A1 NADIA QUIRICI
A1 CINZIA SCAVULLO
A1 UMBERTO GIANELLI
A1 LAURA CORTI
A1 CLAUDIO VITALI
A1 CLODOVEO FERRI
A1 DILIA GIUGGIOLI
A1 ANDREINA MANFREDI
A1 WANDA MAGLIONE
A1 FRANCESCO ONIDA
A1 MICHELE COLACI
A1 SILVANO BOSARI
A1 GIORGIO LAMBERTENGHI DELILIERS
YR 2010
UL http://www.jrheum.org/content/37/10/2053.abstract
AB 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. Conclusion. 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.