Autoimmunity in Scleroderma
485
anti-topo I and anticentromere antibodies
(ACA). The former antibody has been
frequently found in the patients with dif-
fuse scleroderma, while the latter has
been strongly associated with limited scle-
roderma. Furthermore, Fritzler et al. re-
ported that no anti-topo I was found in
more than 127 patients with connective
tissue diseases other than scleroderma,
while ACA was found in only less than
2% of 113 patients with connective tissue
diseases other than scleroderma and Ray-
naud’s disease. In addition, the coexistence
of these two antibodies in the same patient
is very rare. Therefore, both antibodies
show striking disease associations and are
found almost exclusively in patients with
scleroderma.
Nevertheless,
ACA
and
anti-topo
I–positive patients constitute only a half
or
two-thirds
of
scleroderma
patients
(Table 1). The remaining one-third or
another half are patients without ACA or
anti-topo I. Although the latter percentage
may decrease when the detection system
of these autoantibodies is improved, other
autoantibodies are also present in patients
with distinct subsets of scleroderma, and
sometimes even coexist with ACA or
anti-topo I antibody. For example, some
individuals with diffuse scleroderma have
anti-RNA polymerase (RNA polymerase I,
II, III) antibody or anti±brillarin antibody,
and others in overlap with polymyositis
have anti-PM/Scl antibody.
The characterization of these sclero-
derma subset-speci±c autoantibodies will
be helpful in the diagnosis and prognosis
of the patients with scleroderma as well
as in the study on the mechanism of
Tab. 1
Human autoantigens associated with scleroderma.
Antigenic
complex
Autoantibody
frequency in
scleroderma
[%]
Autoantigen
Antigenic
polypeptide
Number
of
residues
B-cell
major
epitope
a
B-cell
minor
epitope
b
T-cell
epitope
Topoisomerase I
50
Topoisomerase I
765
74–139
484–560
658–765
209–386
363–563
Centromere
30
CENP-A
140
3–17
25–38
?
CENP-B
599
1–73
538–599
438–492
?
CENP-C
943
74–244
820–943
396–552
?
HP1
HS
α
191
16–43
106–191
?
PM/Scl
3
PM/Scl-100
885
c
166–245
672–866
?
PM/Scl-75
355
218–355
?
U3 RNP
10
Fibrillarin
321
1–85
149–229
276–321
?
a
,
b
Major and minor epitopes are defned here as the reactive region with
>
50% and
<
50% o± the
corresponding antibodies, respectively.
c
The iso±orm with 860 amino acid residues is also reported.
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