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 or chains or with the same cells expressing PDGFR .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.

Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease / SVEGLIATI BARONI, Silvia; Olivieri, Attilio; Campelli, N; Luchetti, MICHELE MARIA; Poloni, Antonella; Trappolini, S; Moroncini, Gianluca; Bacigalupo, A; Leoni, Pietro; Avvedimento, Ev; Gabrielli, Armando. - In: BLOOD. - ISSN 0006-4971. - 110:1(2007), pp. 237-241. [10.1182/blood-2007-01-071043]

Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease

SVEGLIATI BARONI, SILVIA;OLIVIERI, Attilio;LUCHETTI, MICHELE MARIA;POLONI, Antonella;MORONCINI, Gianluca;LEONI, Pietro;GABRIELLI, ARMANDO
2007-01-01

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 or chains or with the same cells expressing PDGFR .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.
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/53439
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