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Immunology—Autoimmunity 681

TABLE I Examples of the Clinical Diagnostic Specificity of Autoantibodies a
Autoantibody specificity a Molecular specificity Clinical association
Organ-specific autoimmune diseases
Anti-acetylcholine receptor ∗ Acetylcholine receptor Myasthenia gravis
Anti-TSh receptor ∗ TSH receptor Graves’ disease
Antithyroglobulin ∗ Thyroglobulin Chronic thyroiditis
Anti-thyroid peroxidase ∗ Thyroid peroxidase Chronic thyroiditis
Antimitochondria ∗ Pyruvate dehydrogenase complex Primary biliary cirrhosis
Antikeratinoctye ∗ Desmoplakin I homologue Bullous pemphigoid
Antikeratinoctye ∗ Desmoglien Pemphigus foliaceus
Multisystem autoimmune diseases
Anti-double-stranded DNA ∗ B form of DNA SLE
Anti-Sm ∗ B, B , D, and E proteins of U1, U2, and U4–U6 snRNP SLE

Anti-nRNP 70-kDa, A, and C proteins of U1-snRNP MCTD, SLE
Anti-SS-A/Ro 60- and 52-kDa proteins associated with the hY1–Y5 SS, neonatal lupus, SLE
RNP complex
Anti-SS-B/La 47-kDa phosphoprotein complexed with RNA SS, neonatal lupus, SLE
polymerase III transcripts
Anti-Jo-1 ∗ Histidyl tRNA synthetase Polymyositis
Antifibrillarin ∗ 34-kDa protein of box C/D containing snoRNP Scleroderma
(U3, U8, etc.)
Anti-RNA polymerase 1 ∗ Subunits of RNA polymerase 1 complex Scleroderma
Anti-DNA topoisomerase 1 (anti-Scl-70) ∗ 100-kDa DNA topoisomerase I Scleroderma
Anticentromere ∗ Centromeric proteins CENP-A, -B, and -C CREST (limited scleroderma)
cANCA Serine proteinase (proteinase 3) Wegener’s vasculitis

a SLE, systemic lupus erythematosus; MCTD, mixed connective tissue disease; SS, Sj¨ogren’s syndrome; cANCA, cytoplasmic antineutrophil
cytoplasmic antibody; TSH, thyroid-stimulating hormone; CREST, calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly,
telangiectasia. Disease-specific diagnostic marker antibodies indicated by an asterisk.

diseases are components of macromolecular structures SLE. Other autoantibody responses demonstrate similar
such as the nucleosome of chromatin and the small nuclear associations and restrictions. The anti-SS-A/Ro response
ribonucleoprotein (snRNP) particles of the spliceosome, (see Table I) frequently occurs alone in SLE but the anti-
among others. Autoantibodies to different components of SS-B/La response in Sj¨ogren’s syndrome is almost always
the same macromolecular complex can be diagnostic for associated with the anti-SS-A/Ro response. Similarily the
different clinical disorders. For example, the core pro- antichromatin response occurs alone in drug-induced lu-

teins B, B , D, and E, which are components of the U1, pus but is often associated with the anti-dsDNA response
U2, and U4–U6 snRNPs and are antigenic targets in the in idiopathic SLE. Autoantibody specificities may occur
anti-Smith antigen (Sm) response in SLE, are different at different frequencies in a variety of diseases, and the
from the U1 snRNP specific proteins of 70 kDa, A, and resulting profile consisting of distinct groups of autoan-
C, which are targets of the anti-nuclear RNP (nRNP) re- tibodies in different diseases can have diagnostic value.
sponse in mixed connective tissue disease (MCTD; see In some cases the grouping of autoantibody specificities,
Table I). It has also been shown that particular autoanti- such as the preponderance of antinucleolar autoantibod-
body responses are consistently associated with one an- ies in scleroderma (Table I), provides intriguing but as
other. The anti-Sm response, which is diagnostic of SLE, yet little understood relationships with clinical diagnosis.
is commonly associated with the anti-nRNP response, but Unlike SLE, in which a single patient may have multiple
when the anti-nRNP response occurs in the absence of the autoantibody specificities to a number of unrelated nuclear
anti-Sm response it can support the diagnosis of MCTD. autoantigens (e.g., DNA, Sm, SS-A/Ro), scleroderma pa-
These two observations suggest that the snRNP com- tients are less likely to have multiple autoantibody speci-
plexes responsible for the autoantibody response against ficities to nucleolar autoantigens that are unrelated at the
the spliceosome in MCTD may differ from the snRNP macromolecular level (i.e., not part of the same macro-
complexes that produce the antispliceosome response in molecular complex).