|
|
Blood, 1 July 2007, Vol. 110, No. 1, pp. 237-241.
Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2007-01-071043.
 Previous Article | Next Article 
Submitted January 30, 2007
Accepted March 8, 2007
Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease
Silvia Svegliati, Attilio Olivieri, Nadia Campelli, Michele Luchetti, Antonella Poloni, Silvia Trappolini, Gianluca Moroncini, Andrea Bacigalupo, Pietro Leoni, Enrico V. Avvedimento, and Armando Gabrielli*
Dipartimento di Scienze Mediche e Chirurgiche, Sezione di Clinica Medica, Universita Politecnica delle Marche, Ancona, Italy
Dipartimento di Scienze Mediche e Chirurgiche, Sezione di Ematologia, Universita Politecnica delle Marche, Ancona, Italy
Divisione di Ematologia, Ospedale S.Martino, Genoa, Italy
Dipartimento di Biologia e patologia Molecolare e Cellulare, Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Universita Federico II, Naples, Italy
* Corresponding author; email: a.gabrielli{at}univpm.it.
Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that found in patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the PDGF receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoantibodies are also present in patients affected by ecGVHD. Serum from 39 patients subjected to allogeneic stem cell transplantation for haematological malignancies (22 with ecGVHD and 17 without cGVHD) and 20 normal controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR  or  chains or the same cells expressing PDGFR . Stimulatory antibodies to the PDGFR were selectively found in all patients with ecGVHD but in none of the patients without cGVHD. Higher levels were detected in patients with generalized skin involvement and/or lung fibrosis. Antibodies recognized native PDGFR, induced tyrosine phosphorylation, accumulation of reactive oxygen species (ROS), and stimulated type I collagen gene expression through the Ha-Ras-ERK1/2-ROS signalling pathway. The biological activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Stimulating results with stimulatory antibodies
- Markus Y. Mapara
Blood 2007 110: 6-7.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
E Balada, C P Simeon-Aznar, J Ordi-Ros, M Rosa-Leyva, A Selva-O'Callaghan, J Pardos-Gea, V Fonollosa-Pla, and M Vilardell-Tarres
Anti-PDGFR-{alpha} antibodies measured by non-bioactivity assays are not specific for systemic sclerosis
Ann Rheum Dis,
July 1, 2008;
67(7):
1027 - 1029.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Andrae, R. Gallini, and C. Betsholtz
Role of platelet-derived growth factors in physiology and medicine
Genes & Dev.,
May 15, 2008;
22(10):
1276 - 1312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Fujii, G. Cuvelier, K. She, S. Aslanian, H. Shimizu, A. Kariminia, M. Krailo, Z. Chen, R. McMaster, A. Bergman, et al.
Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group
Blood,
March 15, 2008;
111(6):
3276 - 3285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fineschi, F. Cozzi, D. Burger, J.-M. Dayer, P. L. Meroni, and C. Chizzolini
Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts
Rheumatology,
December 1, 2007;
46(12):
1779 - 1785.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
