Identification of nuclear spliceosomal antigens targeted by NOD mouse antibodies following sodium iodide intake.
The non-obese diabetic (NOD) mouse spontaneously develops a range of autoreactive responses including an autoantibody response to nuclear antigens. As elevated dietary iodine has been shown to increase thyroid autoimmune pathology in NOD mice, the effect of sodium iodide (NaI) on the development of anti-nuclear antibodies (ANA) was assessed. Interestingly, the NaI symporter is expressed in both thyroid and salivary glands. Elevated dietary iodine was found to increase the percentage of male NOD mice developing autoantibodies. Specifically, the nuclear autoantibodies that develop in NOD mice were shown to target specific spliceosomal components. The target specificity of the autoantibodies was determined using recombinant spliceosomal proteins and shown to include U1A, U170K, U2B'', U2A', as well as the Sm proteins D1, D2, and B. The autoantibody isotypes most consistently represented were IgG2a and IgG2b.
Thompson
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University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK.
Pomeranz Krummel
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DA
Jacobsen
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Nagai
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K
Cooke
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A
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000097:blood; D000918:Antibody Specificity; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000276:immunology; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology; D012974:Sodium Iodide / Q000008:administration & dosage / Q000633:toxicity*; D017381:Spliceosomes / Q000276:immunology*; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C526408:SNRPB2 protein, human; C075339:U1A protein; D055517:snRNP Core Proteins; D012974:Sodium Iodide