IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified
as topoisomerase 1 distinguishes between limited and diffuse systemic
a de la Pen
Mathieu C. Tamby,
and Luc Mouthon
UPRES EA 3408, UFR-SMBH Le
onard-de-Vinci, Bobigny, France
canismes et Macromole
cules de la Synthe
ique et Cristalloge
se, UPR 9002,
Institut de Biologie Moleculaire et Cellulaire du Centre National de la Recherche Scientifique, Strasbourg, France
Laboratoire d’Immunologie, Hoˆpital Cochin, Assistance Publique-Hoˆpitaux de Paris (AP-HP), Paris, France
Service de Rhumatologie, Hoˆpital Cochin, Paris, France
Service de Rhumatologie, Hoˆpital Bichat, AP-HP, Paris, France
Service de Me
decine Interne, Hoˆpital Pitie
re, AP-HP, Paris, France
Laboratoire de Biologie et The
rapeutique des Pathologies Immunitaires, Hoˆpital Pitie
re, Paris, France
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
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
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 . 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
; anti-topoisomerase 1 (anti-topo 1) Ab, which are
associated with diffuse SSc ; and anti-RNA-polymerase
Ab which are associated with diffuse SSc and renal involve-
ment . Although their pathogenic roles are not clearly
1521-6616/$ - see front matter D 2004 Elsevier Inc. All rights reserved.
* 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: email@example.com (L. Mouthon).
Both authors contributed equally to this study.
Clinical Immunology 111 (2004) 241 – 251