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

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 autoantibody production.