484
Autoimmunity in Scleroderma
cell functions such as cell division, DNA
replication, transcription, and translation.
Although the primary event that triggers
production of autoantibodies is not known,
more than 95% of scleroderma patients
produce autoantibodies to nuclear com-
ponents. Scleroderma (systemic sclerosis)
is a disease characterized by collagen de-
position and subsequent Fbrosis in skin
and internal organs. The extent of Fbrosis
shows considerable variation in severity,
which classiFes scleroderma into two dis-
tinct subtypes: the limited cutaneous form
and diffuse form. In the former, skin thick-
ening is relatively restricted to the Fngers,
hands, and/or face but without extension
to other internal organs. In the latter,
skin changes are widespread and often
rapidly progressive, involving the trunk
and distal and proximal portions of the ex-
tremities with internal organ involvement.
In addition, some patients have overlap-
ping features with other connective tissue
diseases.
ANAs in patients with scleroderma can
be mainly classiFed into antinuclear and
antinucleolar antibodies by immunoflu-
orescence
staining
patterns
of
tissue
culture cells as substrate (±ig. 1). The
former is further subdivided into sev-
eral distinct nuclear staining patterns:
discrete speckles (almost equal to the
centromere), coarse
speckles,
diffusely
grainy,
and
homogeneous.
The
latter
is divided into speckled, homogeneous,
and clumpy. With these distinctive au-
toantibodies, a number of targeted au-
toantigen molecules have been identiFed:
DNA topoisomerase I (topo I, formerly
described as Scl-70), three centromere
proteins (CENP-A, CENP-B, and CENP-
C),
PM/Scl
(polymyositis/scleroderma)-
associated antigens, RNA polymerases,
and Fbrillarin (U3 RNP-associated 34 kDa
peptide).
Among autoantibodies
against
these
antigens, two antibodies have been well
correlated with subtypes of scleroderma:
(a)
(b)
(c)
Fig. 1
Indirect immunofluorescence pictures of HEp-2 cells with scleroderma sera.
(a) Anticentromere antibody. (b) Antitopoisomerase I antibody. (c) AntiFbrillarin
antibody.
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