IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified
as topoisomerase 1 distinguishes between limited and diffuse systemic
sclerosis patients
Paloma Garcı
´
a de la Pen
˜
a-Lefebvre,
a,1
Youri Chanseaud,
a,1
Mathieu C. Tamby,
a
Joseph Reinbolt,
b
Fre
´
de
´
ric Batteux,
c
Yannick Allanore,
d
Andre
´
Kahan,
d
Olivier Meyer,
e
Olivier Benveniste,
f
Olivier Boyer,
g
Loı¨c Guillevin,
h
Marie-Christophe Boissier,
a
and Luc Mouthon
a,h,
*
a
UPRES EA 3408, UFR-SMBH Le
´
onard-de-Vinci, Bobigny, France
b
De
´
partement Me
´
canismes et Macromole
´
cules de la Synthe
`
se Prote
´
ique et Cristalloge
´
ne
`
se, UPR 9002,
Institut de Biologie Moleculaire et Cellulaire du Centre National de la Recherche Scientifique, Strasbourg, France
c
Laboratoire d’Immunologie, Hoˆpital Cochin, Assistance Publique-Hoˆpitaux de Paris (AP-HP), Paris, France
d
Service de Rhumatologie, Hoˆpital Cochin, Paris, France
e
Service de Rhumatologie, Hoˆpital Bichat, AP-HP, Paris, France
f
Service de Me
´
decine Interne, Hoˆpital Pitie
´
-Salpeˆtrie
`
re, AP-HP, Paris, France
g
Laboratoire de Biologie et The
´
rapeutique des Pathologies Immunitaires, Hoˆpital Pitie
´
-Salpeˆtrie
`
re, Paris, France
h
Service de Me
´
decine Interne, Hoˆpital Avicenne, AP-HP et Universite
´
Paris-Nord, Bobigny, France
Received 26 August 2003; accepted with revision 13 January 2004
Available online 1 April 2004
Abstract
We have analyzed antibody (Ab) reactivities of patients with limited systemic sclerosis (SSc) and anti-centromere Ab, patients with
diffuse SSc and anti-topoisomerase 1 (anti-topo 1) Ab, patients with diffuse SSc without anti-topo 1 or anti-centromere Ab and age- and
gender-matched healthy controls with normal human tissue and endothelial cell (EC) antigens.
IgG reactivities with tissue antigens differed significantly between patients with anti-topo 1 Ab and patients with anti-centromere Ab. One
100-kDa band identified as topoisomerase 1 in macrovascular and microvascular EC extracts was recognized by IgG from patients with anti-
topo 1 Ab and 50% of patients without specific Ab. IgG from patients with limited SSc and anti-centromere Ab, but not those of other
patients or controls specifically recognized a 80-kDa band only in microvascular EC. Our results indicate that Ab from patients with limited
or diffuse SSc with or without anti-topo 1 Ab exhibit specific and mutually exclusive reactivity patterns.
D 2004 Elsevier Inc. All rights reserved.
Keywords: Systemic sclerosis; Antibody; Endothelial cell
Introduction
Systemic sclerosis (SSc) is a connective tissue disease
characterized by excessive collagen deposition in the dermis
and internal organs, and by vascular hyperreactivity and
obliterative microvascular phenomena [1]. Many autoanti-
bodies have been identified in the sera of SSc patients.
Some of them are disease-specific, while others are also
detected in the sera of patients with other connective tissue
or vascular diseases. Three autoantibodies are specific to
SSc and mutually exclusive: anti-centromere antibodies
(Ab), which are associated with limited forms of the disease
[2]; anti-topoisomerase 1 (anti-topo 1) Ab, which are
associated with diffuse SSc [3]; and anti-RNA-polymerase
Ab which are associated with diffuse SSc and renal involve-
ment [4]. Although their pathogenic roles are not clearly
1521-6616/$ - see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.clim.2004.01.005
* Corresponding author. Laboratoire d’Immunologie, Pavillon Gustave
Roussy, 4e e
´
tage, UFR Cochin-Port Royal, 8 rue Me
´
chain, 75014, Paris,
France. Fax: +33-1-44-41-25-46.
E-mail address: luc.mouthon@cch.ap-hop-paris.fr (L. Mouthon).
1
Both authors contributed equally to this study.
www.elsevier.com/locate/yclim
Clinical Immunology 111 (2004) 241 – 251