Heterogeneous nuclear RNPs as targets of autoantibodies in systemic rheumatic diseases

Authors

  • Katrijn Op De Beéck,

    1. Catholic University of Leuven, Leuven, Belgium
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    • Ms Op De Beéck and Drs. Maes, Van den Bergh, and Bossuyt have filed a patent application for new methods of diagnosing autoimmune diseases in general and Sjögren's syndrome in particular by identifying the presence of antibodies to specific heterogeneous nuclear RNPs (PCT/BE2010/000061, PCT/BE/2008/000087).

  • Liesbeth Maes,

    1. Catholic University of Leuven, Leuven, Belgium
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    • Ms Op De Beéck and Drs. Maes, Van den Bergh, and Bossuyt have filed a patent application for new methods of diagnosing autoimmune diseases in general and Sjögren's syndrome in particular by identifying the presence of antibodies to specific heterogeneous nuclear RNPs (PCT/BE2010/000061, PCT/BE/2008/000087).

  • Karolien Van den Bergh,

    1. Catholic University of Leuven, Leuven, Belgium
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    • Ms Op De Beéck and Drs. Maes, Van den Bergh, and Bossuyt have filed a patent application for new methods of diagnosing autoimmune diseases in general and Sjögren's syndrome in particular by identifying the presence of antibodies to specific heterogeneous nuclear RNPs (PCT/BE2010/000061, PCT/BE/2008/000087).

  • Rita Derua,

    1. Catholic University of Leuven, Leuven, Belgium
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  • Etienne Waelkens,

    1. Catholic University of Leuven, Leuven, Belgium
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  • Kristel Van Steen,

    1. University of Liège, Liège, Belgium
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  • Pieter Vermeersch,

    1. Catholic University of Leuven, Leuven, Belgium
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  • René Westhovens,

    1. University Hospitals Leuven, Leuven, Belgium
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  • Kurt De Vlam,

    1. University Hospitals Leuven, Leuven, Belgium
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  • Patrick Verschueren,

    1. University Hospitals Leuven, Leuven, Belgium
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  • Herbert Hooijkaas,

    1. Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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  • Daniel Blockmans,

    1. University Hospitals Leuven, Leuven, Belgium
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  • Xavier Bossuyt

    Corresponding author
    1. Catholic University of Leuven, Leuven, Belgium
    • Experimental Laboratory Medicine, Immunology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium
    Search for more papers by this author
    • Ms Op De Beéck and Drs. Maes, Van den Bergh, and Bossuyt have filed a patent application for new methods of diagnosing autoimmune diseases in general and Sjögren's syndrome in particular by identifying the presence of antibodies to specific heterogeneous nuclear RNPs (PCT/BE2010/000061, PCT/BE/2008/000087).

    • Dr. Bossuyt is a senior clinical investigator of the Fund for Scientific Research–Flanders.


Abstract

Objective

To investigate the abundance of autoantibodies to heterogeneous nuclear RNPs (hnRNPs) in systemic rheumatic diseases.

Methods

Recombinant human hnRNPs A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these antigens were determined by Western blotting and by enzyme-linked immunosorbent assay (ELISA) (for hnRNPs B1, E1, F, and H1) in serum samples obtained from patients with chronic fatigue syndrome (control subjects) and from patients with various connective tissue diseases.

Results

Western blotting analysis in 106 control subjects and 298 patients with a connective tissue disease revealed that antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more prevalent in patients with Sjögren's syndrome (SS) than in control subjects. The highest reactivity was observed for hnRNPs B1, E1, F, and H1 (reactivity in >45% of patients with SS and in 2.8% of control subjects). Reactivity with hnRNPs B1, E1, F, and H1 was also evaluated by ELISA in 89 control subjects and 228 patients with a connective tissue disease. Reactivity with at least 2 of the 4 tested antigens was observed in 1.1% of control subjects, 16% of patients with systemic lupus erythematosus (SLE), and 18% of patients with SS. Reactivity with at least 3 of the 4 antigens was observed in 0% of the control subjects, 3.2% of patients with SLE, and 15% of patients with SS.

Conclusion

Several hnRNPs are target antigens in SS. The combined presence of antibodies to several hnRNPs was strongly associated with connective tissue disease in general and with SS in particular.

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