Epidermal synthesis and expression of HLA-DR on keratinocytes in lupus erythematosus

It has been suggested that aberrant expression of HLA-DR plays an important role in the induction of an autoimmune reaction. In lupus erythematosus (LE), skin represents a major target for autoimmune attack. We therefore tested lesional and nonlesional skin from 11 patients with different clinical subtypes of LE for the presence of HLA-DR molecules on keratinocytes using a monoclonal antibody against a non-polymorphic HLA-DR determinant. In all lesions tested, HLA-DR-positive keratinocytes were present, whereas in nonlesional skin, these cells remained HLA-DR negative. To exclude the possibility of passive absorption of DR molecules, the de novo synthesis of HLA-DR was demonstrated by the presence of cytoplasmic HLA-DR γ chains in keratinocytes. If aberrant HLA-DR expression is a primary event, it could facilitate the recognition of autoantigens on keratinocytes by immunocompetent cells. Alternatively, the synthesis of DR molecules could be induced as a secondary event by mediators derived from the inflammatory infiltrate.