464
Autoantibodies and Autoimmunity
the non–organ-specifc autoimmune dis-
ease systemic lupus erythematosus (SLE),
anti–double-stranded DNA (dsDNA) auto-
antibodies have been shown to participate
in pathogenic events by way oF com-
plexing with their cognate antigen to
cause immune complex–mediated inflam-
mation. These examples show that in
both the organ-specifc and systemic au-
toimmune diseases,
in vivo
disposition oF
autoantibody in tissues and organs has
clinical signifcance inasmuch as it indi-
cates sites oF inflammation, which may
contribute to the pathological process.
Moreover, detection oF autoantibody de-
posits in the organ-specifc autoimmune
diseases has particular signifcance be-
cause some organ-specifc autoantibodies
have been Found to be the direct mediators
oF pathological lesions. In most autoim-
mune diseases, however, it has not been
determined whether autoantibodies cause
or contribute to disease or are merely a
secondary consequence oF the underlying
clinical condition.
2
Autoantibodies as Diagnostic Markers
The diseases associated with autoantibod-
ies can be divided into two broad groups:
the organ-specifc autoimmune diseases,
in which autoantibodies have the abil-
ity to react with autoantigens From a
particular organ or tissue, and the mul-
tisystem autoimmune diseases, in which
autoantibodies react with common cellular
components that appear to bear little rele-
vance to the underlying clinical picture. In
both cases, particular autoantibody speci-
fcities can serve as diagnostic markers
(Table 1).
In the multisystem autoimmune dis-
eases, there are several Features oF the
relationship between autoantibody speci-
fcity and diagnostic signifcance that bear
consideration. Autoantigens in these dis-
eases are components oF macromolecu-
lar structures such as the nucleosome
oF chromatin and the small nuclear ri-
bonucleoprotein (snRNP) particles oF the
spliceosome, among others. Autoantibod-
ies to diFFerent components oF the same
macromolecular complex can be diagnos-
tic For diFFerent clinical disorders. Thus,
the core proteins B, B
0
,D,andE,whichare
components oF the U1, U2, and U4–U6
snRNPs and are antigenic targets in the
anti-Smith antigen (Sm) response in SLE,
are diFFerent From the U1 snRNP–specifc
proteins oF 70 kDa, A and C, which are
targets oF the anti-nRNP response in
mixed connective tissue disease (MCTD;
see Table 1). It has also been observed
that certain autoantibody responses are
consistently associated with one another.
The anti-Sm response, which is diagnostic
oF SLE, is commonly associated with the
anti-nRNP response, but the anti-nRNP
response can occur without the anti-Sm
response, in which case it can be diag-
nostic oF MCTD. These two observations
suggest that the snRNP complexes respon-
sible For the autoantibody response against
the spliceosome in MCTD may diFFer From
the snRNP complexes that produce the
antispliceosome response in SLE. Other
autoantibody responses demonstrate sim-
ilar
associations
and
restrictions.
The
anti-SS-A/Ro response (see Table 1) Fre-
quently occurs alone in SLE, but the
anti-SS-B/La response in Sj¨ogren’s syn-
drome is almost always associated with
the anti-SS-A/Ro response. Similarly, the
antichromatin response occurs alone in
drug-induced lupus but is usually asso-
ciated with the anti-dsDNA response in
idiopathic SLE.
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