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, Armando Gabrielli

Research output: Contribution to journalArticle

174 Citations (Scopus)

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 languageEnglish
Pages (from-to)237-241
Number of pages5
JournalBlood
Volume110
Issue number1
DOIs
Publication statusPublished - Jul 1 2007

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Platelet-Derived Growth Factor Receptors
Graft vs Host Disease
Grafts
Autoantibodies
Fibroblasts
Fibrosis
Systemic Scleroderma
Reactive Oxygen Species
Skin
Transplantation (surgical)
Phosphorylation
Antibodies
Collagen Type I
Stem cells
Gene expression
Stem Cell Transplantation
Hematologic Neoplasms
Tyrosine
Immunoglobulin G
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Svegliati, S., Olivieri, A., Campelli, N., Luchetti, M., Poloni, A., Trappolini, S., ... Gabrielli, A. (2007). Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood, 110(1), 237-241. https://doi.org/10.1182/blood-2007-01-071043

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 journalArticle

Svegliati, S, Olivieri, A, Campelli, N, Luchetti, M, Poloni, A, Trappolini, S, Moroncini, G, Bacigalupo, A, Leoni, P, Avvedimento, EV & Gabrielli, A 2007, 'Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease', Blood, vol. 110, no. 1, pp. 237-241. https://doi.org/10.1182/blood-2007-01-071043
Svegliati S, Olivieri A, Campelli N, Luchetti M, Poloni A, Trappolini S et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood. 2007 Jul 1;110(1):237-241. https://doi.org/10.1182/blood-2007-01-071043
Svegliati, Silvia ; Olivieri, Attilio ; Campelli, Nadia ; Luchetti, Michele ; Poloni, Antonella ; Trappolini, Silvia ; Moroncini, Gianluca ; Bacigalupo, Andrea ; Leoni, Pietro ; Avvedimento, Enrico V. ; Gabrielli, Armando. / Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. In: Blood. 2007 ; Vol. 110, No. 1. pp. 237-241.
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