Diverse Antibody Recognition Patterns of the Multiple Sm-D Antigen Polypeptides

Anti-Sm antibodies are intrinsically associated with systemic lupus erythematosus. The major targets are the so-called B and D polypeptides. The number of Sm targets increased upon the report that SDS–PAGE conditions could be manipulated to display not one, but three Sm-D polypeptides. To characterize the relative reactivities of Sm-D1, Sm-D2, and Sm-D3, both human and murine autoantibodies were screened. These sera displayed two distinct patterns of reactivity. The Sm-D1/D3 pattern was at least four times more common than Sm-D1/D2/D3 recognition. The predominant immunoreactive protein was Sm-D1. We screened over 40 monoclonal antibodies that were derived from MRL mice and were selected as anti-Sm positive. Of these, 27 reacted with at least one Sm-D polypeptide by protein blot, but in contrast to the MRL sera, none of these antibodies reacted with Sm-D2. Rather, there were two recognition patterns of approximately equal abundance, against Sm-D1/D3 or Sm-D1 alone. Last, we explored the immune response to isolated Sm-D (containing all three D antigens) from rabbit thymus. The autoantibody produced reacted only with Sm-D2. There is accumulating evidence that the anti-Sm response is at least partially antigen-driven. The details of the intragroup relationships within the Sm-D family of proteins provide further insight into the Sm autoimmune response.