Human systemic lupus erythematosus sera contain antibodies against cell-surface protein(s) that share(s) epitope(s) with DNA.

In previous work, a murine monoclonal anti-DNA antibody (PME77) with specificity for double-stranded DNA has been found to bind five polypeptides (34, 33, 17, 16, and 14 kDa) that are expressed at the surface of several human cell types involved in lupus pathogenesis. To determine more precisely the nature of the antigens recognized by the PME77 monoclonal antibody, and to release cell-surface-accessible fragments, we used a mild, controlled elastase treatment. We isolated several of these polypeptides by immunoaffinity chromatography. A polyclonal antibody was prepared by immunizing a rabbit with a mixture of these polypeptides (17, 16, and 14 kDa) adsorbed on nitrocellulose. This antibody was shown to react with 17-, 16-, and 14-kDa polypeptides. This antibody does not bind to double-stranded DNA, suggesting that most of the immunogenic determinants of these polypeptides are not shared by double-stranded DNA. Of six human systemic lupus erythematosus sera tested, all contained antibodies that recognized this cell-surface protein(s) and crossreacted with double-stranded DNA. We suggest that this protein(s) be called LAMP [lupus-associated membrane protein(s)].