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Fluorescence patterns of nuclear autoantigens

Autoantibodies recognizing non-chromatin related proteins




non-chromatin image


The genetic information of DNA is transcribed to precursor mRNA (heterogeneous nuclear RNA, hnRNA). The small nuclear RNAs (small nuclear RNA, snRNA) such as U1, U2, U4/U6 and U5 RNA are involved in the splicing of hnRNA. These RNAs are complexed with proteins to form ribonucleoproteins (RNPs).


Anti-U1RNP antibody


photo 21


Pattern Coarse speckled (larger granular) nuclear pattern with no nucleolar and cytoplasmic staining. The chromosomal regions do not stain in mitotic cells.
Antigen 3 kinds of polypeptides bound to U1 RNA; U1RNP-68kD, U1RNP-A(34kD), U1RNP-C(23kD)
Other analytical method DID, ELISA, WB, Immunoprecipitation, CLEIA
Clinical significance The presence of the antibodies to U1RNP constitute one of major diagnostic criteria for MCTD.
References 15, 16

Anti-Sm antibody


photo 22     AF/CDC-5*

Pattern Coarse speckled staining similar to those of anti-U1RNP antibody.
Antigen U1, U2, U4/U6 and U5 RNA-bound proteins with 5 kinds of epitopes, B'/B(29kD/28kD), D(16kD), E(12kD), F(11kD) and G(10kD). The main epitopes comprise B'/B and D polypeptides. Antibodies to E-F-G complex as dominant epitopes are also reported.
Other analytical method DID, ELISA, WB, Immunoprecipitation, CLEIA
Clinical significance Marker antibody for SLE. The presence of anti-Sm antibody is included in the criteria for the classification of SLE by the American College of Rheumatology.
References 17



Anti-U2RNP antibody / Anti-U1U2RNP antibody



photo 23


Pattern Coarse speckled nuclear staining similar to those of anti-U1RNP antibody.
Antigen U2RNA-bound proteins with 2 kinds of epitopes on A'(32kD) and B"(28.5kD).
Since B" and A polypeptides of U1RNP have common epitopes, U2 RNP antibody targeting B" also reacts with U1RNP (anti-U1U2RNP antibody).
Other analytical method Immunoprecipitation
Clinical significance Polymyositis/scleroderma overlap syndrome
References 3, 15, 16



Anti-hnRNP antibody


photo 24


Pattern Large speckled (granular) nucleoplasmic staining with no chromosomal fluorescence in mitotic cells. The antibodies frequently coexist with anti-U1RNP and anti-Sm antibodies, and give coarse speckled patterns.
Antigen hnRNA bound proteins-A/B, A1, A2, C, I
Other analytical method ELISA, WB
Clinical significance These antibodies were first reported in patients with MCTD. Antibodies to the A/B polypeptides and those to the A1 and A2 polypeptides occur in SLE and rheumatoid arthritis, respectively. Recently, anti-hnRNP-I antibodies with weak nuclear staining specific for scleroderma and anti-hnRNP-C antibodies with speckled nuclear staining in scleroderma were reported.
References 18, 19, 20, 21



Anti-SS-A/Ro antibody


photo 25    AF/CDC-7*


Pattern Fine speckled nuclear staining observed in acetone-fixed slides, but not in alcohol-fixed ones. The chromosomal region shows no fluorescence in mitotic cells.
Antigen Y1-Y5RNA-bound proteins (52kD, 60kD)
Other analytical method DID, ELISA, WB, Immunoprecipitation, CLEIA
Clinical significance These antibodies occur most frequently in patients with SS, and those with SLE. Sometimes found in patients with rheumatoid arthritis, myositis or scleroderma. The presence of the antibodies in the mother is associated with neonatal lupus and congenital heart block. The presence of anti-SS-A antibodies constitutes one of the diagnostic criterion of SS in Europe.
References 22



Anti-SS-B/La antibody


photo 26     AF/CDC-2*


Pattern Fine dense speckled nuclear staining is observed in interphase cells with no chromosomal fluorescence in mitotic cells.
Antigen 48 kD SS-B/La protein, a termination factor for RNA polymerase III transcription
Other analytical method DID, ELISA, WB, Immunoprecipitation, CLEIA
Clinical significance The antibodies are found in patients with SS and SLE. As with anti-SS-A antibodies, the presence of these antibodies is associated with neonatal lupus and congenital heart block. The antibodies were reported to be frequently positive in patients with recurrent annular erythema. The presence of anti-SS-B antibodies constitutes one of the diagnostic criterion of SS in Europe.
References 23


Anti-p80 coilin antibody


photo 27

Pattern Granular or few nuclear dots staining**, 0 to 6 dots (ave. 2 dots) per nucleus fluorescence. The distinct large dotty fluorescence can be seen in cells during S and G2 phases, and mitotic cells show no staining.
Antigen p80 coilin, the 80kD protein composing the coiled body in nucleoplasm.
Other analytical method WB
Clinical significance These antibodies occur in some patients with SS and those with primary biliary cirrhosis.
References 24, 25


Anti-Sp100 antibodies


photo 28

Pattern Granular or multiple (1 to 24) nuclear dots staining**.
Antigen Sp100 protein. Multiple nuclear dots staining is also observed by the antibodies to promyelocytic leukemia (PML) protein, NDP53 (a binding protein to PML oncogenic domain including Sp100).
Other analytical method WB
Clinical significance These antibodies occur in some patients with PBC.
References 26, 27, 28

* Reference serum from Centers for Disease Control
** Since the numbers of staining dots seen in few nuclear dots and multiple nuclear dots patterns overlap each other, it is sometimes difficult to distinguish these patterns. These patterns are often called granular or nuclear dots patterns.



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SLE: systemic lupus erythematosus, SSc: systemic sclerosis, MCTD: mixed connective tissue disease, SS: Sjögren's syndrome, PM/DM: polymyositis/dermatomyositis, RA: rheumatoid arthritis, PBC: primary biliary cirrhosis, AIH: autoimmune hepatitis


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