AUTOANTIBODIES TO DESMOPLAKIN-I AND DESMOPLAKIN-II IN PATIENTS WITH ERYTHEMA-MULTIFORME

Erythema multiforme (EM) represents a syndrome of chronic recurrent in flammatory skin disease. Depending on the severity and extent of skin and mucosal involvement, it is defined either as EM minor or EM major. In this study we demonstrate the presence of autoantibodies (aAbs) ag ainst desmoplakin I and II, two major proteins of the desmosomal plaqu e, in six of six patients with the severe variant of EM, EM major. Lig ht microscopic studies of lesional skin and mucous membranes localized in vivo bound immunoglobulin G (IgG) in a dotted desmosomal pattern a long the cytoplasmic membranes of keratinocytes. By immunoelectronmicr oscopy, in vivo bound IgG was confined to the desmosomal plaques. Thes e findings were confirmed by indirect immunolocalization studies that demonstrated the presence of IgG aAbs in the serum of patients during active disease. These aAbs did not only bind to desmosomal plaques of epithelial cells where they colocalized with defined murine monoclonal antibodies directed against desmoplakin I and II, but also labeled th e intercalated discs of myocardial cells. Biochemical characterization of circulating IgG aAbs revealed desmoplakin I and II as actual targe t autoantigens. By passive transfer of serum into newborn mice, in viv o binding of serum aAbs to keratinocytes was shown. The findings prese nted in this study imply a humoral immune response in certain patients with EM major and indicate a potential pathogenetic role of aAbs agai nst desmoplakin I and II in this disease.