S-27
1
Cardeza Foundation for Hematologic
Research, Jefferson Medical College of
Thomas Jefferson University, Philadelphia,
PA, USA;
2
Rheumatology Division,
Cerrahpasa Medical Faculty, University
of Istanbul;
3
Electro-Neurophysiology
Research and Application Centre, Univer-
sity of Istanbul, Istanbul;
4
Rheumatology
Division, Gulhane School of Medicine,
Ankara, Turkey.
Ayhan Dinc, MD, Associate Professor;
Toshiro Takafuta, MD, PhD, Assistant
Professor; Dongsheng Jiang, MD;
Melike Melikoglu, MD; Guher-Saruhan
Direskeneli, MD, Associate Professor;
Sandor S. Shapiro MD, Professor.
Please address correspondence to:
Ayhan Dinc, MD, Rheumatology Division,
Gulhane School of Medicine, 06010 Etlik,
Ankara, Turkey.
E-mail: adinc@gata.edu.tr
Received on June 26, 2002; accepted in
revised form on November 25, 2002.
Clin Exp Rheumatol 2003; 21 (Suppl. 30):
S27-S30.
© Copyright CLINICAL AND EXPERIMEN-
TAL RHEUMATOLOGY 2003.
Key words: Behçet’s disease, anti-
endothelial antibodies, endothelium.
ABSTRACT
Objective. Circulating antibodies that
bind to human endothelial cells cul -
tured in vitro have been detected in a
variety of diseases, including Behçet’s
disease. In this disorder the reported
prevalence of AECA has varied widely.
One likely source of variability is the
ELISA assay itself, in which differing
conditions and reagents have been
used in different reports.
Methods. We have re-examined the fre -
quency of AECA in 132 Turkish
Behçet’s patients and 50 healthy Turk -
ish controls, comparing several dif -
ferent methods of preparing the target
endothelial cells. Human umbilical
vein endothelial cells (HUVEC) were
used either: 1) fresh and non-treated,
2) fixed, or 3) TNF -stimulated. All
stages of the procedures were per -
formed at room temperature.
Results. In Behçet’s patients, using
fresh, non-treated HUVEC, 17 of 130
(13.1%) and 9 of 132 (6.8%) sera were
positive for IgG- and IgM-AECA,
respectively. However, among 50 nor -
mal controls, 2 (4.0%) had IgG-posi -
tive and 4 (8.0%) had IgM-positive
ELISAs under the same conditions. The
difference in the frequency of positives
between patients and controls was not
statistically significant. Fixed HUVEC
and TNF -treated HUVEC gave simi -
lar results as well. When group means
were examined, only the mean for IgG-
AECA determined with TNF -stimulat -
ed HUVEC reached statistical signifi -
cance.
Conclusion. The discrepancy between
our data and earlier reports in the lit -
erature probably reflects the method -
ological differences alluded to, and
highlights the difficulties in interpret -
ing ELISA assays for AECA.
Introduction
Behçet’s disease (BD) is a condition of
unknown etiology, which is characteri-
zed by recurrent orogenital ulceration,
skin lesions and an inflammatory arth-
ritis, as well as by vasculitic involve-
ment of the major peripheral arteries
and the veins and vessels of the central
nervous system (1). The vascular invol-
vement of BD includes thrombophle-
bitis, seen in about 25% of patients,sel-
dom if ever with embolization, and ar-
teritis with occlusion and aneurysm
formation (2). This has suggested the
existence of a hypercoagulable state in
BD patients, and has raised the possi-
bility of a role for the endothelium in
the pathogenesis of BD. Indeed, previ-
ous studies in Behçet’s disease have
been interpreted to show evidence of
endothelial dysfunction (3-5), and sev-
eral studies have found AECA in 18-
37% of BD patients (6-12). However, a
number of methodological differences
exist between these studies, making it
difficult to compare their results. Some
studies, for example, were performed at
37ºC, a temperature at which surface-
bound IgG can be internalized (13),
while others have not taken into ac-
count the possible occurrence of hete-
rophil antibodies that might have aug-
mented the apparent specific binding in
ELISA (14). Such variations have sug-
gested a need for standardized tests for
AECAs (15). In the present study, we
measured AECA by ELISA in a large
group of Behçet’s patients and controls,
and examined the significance of sever-
al variables in the methodology.
Materials and methods
Source of sera
Sera were obtained from 132 Turkish
patients with BD attending three cen-
ters in Turkey (Cerrahpasa and Istanbul
Medical Faculties, University of Istan-
bul and Gulhane School of Medicine,
Ankara) and from 50 healthy Turkish
controls. All patients fulfilled the ISG
criteria for diagnosis of BD (16). The
clinical features of the patients are
shown in Table I.
The control group consisted of 22 fe-
males and 28 males,with a mean age of
27.7 ± 8.4 years (range 19-49 years).
Anti-endothelial cell antibodies in Behçet’s disease
A. Dinc
1,4
, T. Takafuta
1
, D. Jiang
1
, M. Melikoglu
2
, G. Saruhan-Direskeneli
3
, S.S. Shapiro
1