Autoimmunity in Scleroderma
487
central role in the pairing and disjunc-
tion of daughter chromosomes in mitosis
and meiosis. The human centromere at the
metaphase chromosome has a trilaminar
disk-shaped structure that was revealed on
electromicroscopic observation, which is
called the
kinetochore
.
Moroi
et al.
Frst
reported
ACA
in
the sera of patients with scleroderma
in 1980. ACA is recognized as a ‘‘dis-
ease marker’’ antibody of limited cu-
taneous
scleroderma,
which
was
for-
merly called
CREST syndrome
. In addi-
tion, ACA are indispensable probes for
the analysis of the structure of the cen-
tromere/kinetochore.
The II± pattern by ACA is discrete
speckled nucleoplasmic staining in in-
terphase cells and strong centromeric
dots decorated in the metaphase plate
(±ig. 1a). Three major target autoantigens,
cen
tromere
p
rotein (CENP)-A, B, and C,
have been identiFed with ACA-positive
sera. Earnshaw et al. Frst isolated cDNA
encoding CENP-B, the 80 kDa human
centromere autoantigen, by expression
cloning. Next, Saitoh et al. isolated cDNA
clones that encode the human CENP-C,
140 kDa human centromere autoantigen,
with immunoscreening. As for CENP-A,
the 17 kDa histone-like centromere anti-
gen, Sullivan et al. cloned its bovine cDNA
using PCR with degenerated oligonu-
cleotides derived from the amino acid
sequences previously reported by Palmer
et al. and isolated its human homologue.
These three antigens exist in the cen-
tromere during cell cycles (±ig. 2). In
contrast, the 330 kDa CENP-± antigen lo-
calizes in the centromere from metaphase
Microtubules
Kinetochore
Pairing
domain
Central
domain
Inner plate
Outer plate
CENP-F
Fibrous
corona
CENP-A
CENP-C
CENP-H
CENP-E
CENP-B
HP1
HS
a
INCENPs
Fig. 2
Centromere domain and centromere antigens. Elements of centromeric region are
depicted mainly for CENPs and autoantigens. Centromere proteins are divided into two
groups: one is the constitutive proteins, for example, CENP-A, -B, -C, and -H, and another is
the chromosome passenger proteins, for example, CENP-E and -F. Some proteins shown
here have not been reported as autoantigens, for example, CENP-H and INCENPs.
previous page 487 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 489 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off