Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis.
OBJECTIVE
Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc.


METHODS
Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center.


RESULTS
Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal.


CONCLUSIONS
The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.
Classen
Jean-François
JF
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Henrohn
Dan
D
Rorsman
Fredrik
F
Lennartsson
Johan
J
Lauwerys
Bernard R
BR
Wikström
Gerhard
G
Rorsman
Charlotte
C
Lenglez
Sandrine
S
Franck-Larsson
Karin
K
Tomasi
Jean-Paul
JP
Kämpe
Olle
O
Vanthuyne
Marie
M
Houssiau
Frédéric A
FA
Demoulin
Jean-Baptiste
JB