Abstract
Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (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 hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR α or β chains or with the same cells expressing PDGFR α. Stimulatory antibodies to the PDGFR were found selectively 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 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
| Original language | English |
|---|---|
| Pages (from-to) | 237-241 |
| Number of pages | 5 |
| Journal | Blood |
| Volume | 110 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 1 2007 |
Fingerprint
ASJC Scopus subject areas
- Hematology
Cite this
Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. / Svegliati, Silvia; Olivieri, Attilio; Campelli, Nadia; Luchetti, Michele; Poloni, Antonella; Trappolini, Silvia; Moroncini, Gianluca; Bacigalupo, Andrea; Leoni, Pietro; Avvedimento, Enrico V.; Gabrielli, Armando.
In: Blood, Vol. 110, No. 1, 01.07.2007, p. 237-241.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease
AU - Svegliati, Silvia
AU - Olivieri, Attilio
AU - Campelli, Nadia
AU - Luchetti, Michele
AU - Poloni, Antonella
AU - Trappolini, Silvia
AU - Moroncini, Gianluca
AU - Bacigalupo, Andrea
AU - Leoni, Pietro
AU - Avvedimento, Enrico V.
AU - Gabrielli, Armando
PY - 2007/7/1
Y1 - 2007/7/1
N2 - Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (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 hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR α or β chains or with the same cells expressing PDGFR α. Stimulatory antibodies to the PDGFR were found selectively 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 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
AB - Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (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 hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR α or β chains or with the same cells expressing PDGFR α. Stimulatory antibodies to the PDGFR were found selectively 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 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
UR - http://www.scopus.com/inward/record.url?scp=34347386226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347386226&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-01-071043
DO - 10.1182/blood-2007-01-071043
M3 - Article
VL - 110
SP - 237
EP - 241
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -