Antiendothelial cell antibodies induce apoptosis of bone marrow endothelial progenitors in systemic sclerosis

Nicoletta Del Papa, Nadia Quirici, Cinzia Scavullo, Umberto Gianelli, Laura Corti, Claudio Vitali, Clodoveo Ferri, Dilia Giuggioli, Andreina Manfredi, Wanda Maglione, Francesco Onida, Michele Colaci, Silvano Bosari, Giorgio Lambertenghi Deliliers

Research output: Contribution to journalArticle

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. 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. The Journal of Rheumatology Copyright

Original languageEnglish
Pages (from-to)2053-2063
Number of pages11
JournalJournal of Rheumatology
Volume37
Issue number10
DOIs
Publication statusPublished - Oct 2010

Keywords

  • Antiendothelial cell antibodies
  • Apoptosis
  • Bone marrow
  • Systemic sclerosis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

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  • Cite this

    Del Papa, N., Quirici, N., Scavullo, C., Gianelli, U., Corti, L., Vitali, C., Ferri, C., Giuggioli, D., Manfredi, A., Maglione, W., Onida, F., Colaci, M., Bosari, S., & Deliliers, G. L. (2010). Antiendothelial cell antibodies induce apoptosis of bone marrow endothelial progenitors in systemic sclerosis. Journal of Rheumatology, 37(10), 2053-2063. https://doi.org/10.3899/jrheum.091346