41 research outputs found

    60 kD Ro and nRNP A Frequently Initiate Human Lupus Autoimmunity

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    Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns

    Autoantibodies precede lupus classification and occur in linked subsets.

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    <p>Kaplan-Maier survival curves for the onset of each autoantibody specific as measured by a solid phase, bead-based assay are presented. Anti-60 kD Ro, anti-La and anti-52 kD Ro are among the earliest specificities detected by this method. In contrast, anti-68 kD nRNP and nRNP A specificities are frequently detected closer to the time of lupus classification.</p

    Potential mechanism for development of autoantibodies through a common environmental etiology.

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    <p>While potential structural mimics are known with EBNA-1 for Ro, Sm B, Sm D, nRNP A, nRNP C and nRNP 70 K, no such structural relationship is known for a heteroimmune response operating to generate anti-dsDNA, anti-chromatin or anti-ribosomal P.</p
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