Autoimmunity in Scleroderma
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Scleroderma is a multisystem connective tissue disease of unknown etiology
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organs, and microvascular obliteration.
Several autoantibodies against cellular
components are striking features of scleroderma and some are associated with
certain clinical subsets. This article mainly reviews the autoimmune phenomenon
against centromere antigens and topoisomerase-I, which are commonly found in
the limited skin sclerosis type and the proximal type respectively. For the production
of autoantibodies, molecular mimicry hypothesis and implications of apoptosis are
also discussed.
1
Scleroderma and Autoantibodies
1.1
Methods of Autoantibody Detection
Sera from human autoimmune patients
contain autoantibodies that react with
many important cellular antigens. De-
tection of antinuclear antibody (ANA) is
widely accepted as an important test in the
diagnosis of many connective tissue dis-
eases such as systemic lupus erythemato-
sus, scleroderma, Sj¨ogren’s syndrome, and
polymyositis. ANA testing by indirect im-
munofluorescence (IIF) is commonly used
as a broad screen for the detection of a vari-
ety of autoimmune diseases. Initially, ANA
tests by IIF methods were performed on
mouse kidney or rat liver tissue sections,
but lately many laboratories use HEp-2 hu-
man larynx epithelioma cancer cell line as
substrate. Human cultured cells are better
for the detection of human and prolifer-
ating nuclear antigens. In contrast to a
few speci±c fluorescent patterns for par-
ticular antigens, the main patterns in IIF
studies are not speci±c for any autoanti-
bodies or disease entity. Characterization
of the speci±c antibodies using double
immunodiffusion
assay, enzyme-linked
immunosorbent assay (ELISA), or im-
munoblotting with appropriate reference
sera is necessary. Immunoblotting with an
extract from cultured cells is a very sensi-
tive assay and permits detection of autoan-
tibodies against soluble and insoluble anti-
gens. This method has proved useful in a
number of studies to characterize many au-
toantigens. Since expression cloning was
±rst applied to isolation of autoantigens
in 1985, cloned autoantigens themselves
have been used for diagnostic autoan-
tibody determination, molecular analysis
of autoimmune epitopes, and molecular
investigation of autoimmune processes.
More recently, many clinical laboratories
use commercial ELISA kits with cloned re-
combinant autoantigens, which are often
expressed by
E. coli
. Although there might
be the lack of proper folding or protein
modi±cation of some recombinant pro-
teins obtained from prokaryotic sources,
ELISA is highly sensitive, quantitative, and
suitable for simultaneous analysis of a
large number of serum samples, providing
substantial cost and time savings.
1.2
Clinical Subsets of Scleroderma and
Autoantibodies
Connective tissue disease patients have
various autoantibodies against a variety of
cellular components required for universal
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