A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G Sm snRNP proteins as an E-F-G complex but not in their denatured states
Hero Brahms PhD
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Search for more papers by this authorVeronica A. Raker MSc
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Search for more papers by this authorWalther J. van Venrooij MSc, PhD
University of Nijmegen, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
Reinhard Lührmann PhD
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Emil Mannkopff Strasse 2, Marburg 35033, GermanySearch for more papers by this authorHero Brahms PhD
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Search for more papers by this authorVeronica A. Raker MSc
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Search for more papers by this authorWalther J. van Venrooij MSc, PhD
University of Nijmegen, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
Reinhard Lührmann PhD
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Emil Mannkopff Strasse 2, Marburg 35033, GermanySearch for more papers by this authorAbstract
Objective. To determine whether the E, F, and G Sm proteins present antigenic determinants recognized by systemic lupus erythematosus (SLE) patient sera, and if so, whether the antigenicity depends on the native conformations of the polypeptides and/or is E-F-G complex restricted.
Methods. Radioimmunoprecipitation, epitope tagging, expression polymerase chain reaction, in vitro translation, in vitro reconstitution, and immunoblotting.
Results. Most of the anti-Sm SLE patient sera tested reacted with one or more of the E, F, and G proteins in immunoprecipitation studies but not on immunoblots. All sera, however, highly efficiently immunoprecipitated the E-F-G complex. This complex recognition was detected exclusively in anti-Sm patient sera but not in patient sera with other serotypes.
Conclusion. We demonstrate the presence of a novel and abundant anti-Sm autoantibody class in SLE patient sera which exclusively or predominantly recognizes conformational Sm epitopes present on the E-F-G complex but not on the denatured proteins. This complex recognition is highly specific for sera of the anti-Sm serotype and may be relevant for clinical diagnosis as well as for understanding the etiology of anti-Sm auto-antibody production.
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