Autoantibodies Against Desmoplakin I and II Define a Subset of Patients with Erythema Multiforme Major

Abstract

In a previous report, we described autoantibodies against the desmosomal plaque proteins desmoplakin I and II (dp I and II) in patients with erythema multiforme (EM) major. In the present study we investigated ten EM major and eight EM minor patients for circulating autoantibodies and performed clinical and immunomorphological evaluations. Seven out of ten EM major patients revealed anti-dp I and II autoantibodies. Antigens were biochemically characterized by Western blotting and immunoprecipitation of epithelial-cell-derived protein extracts. These autoantibodies bind in vivo to lesional skin/mucosa in a pemphigus-type dotted pattern along the cytoplasmic membranes of keratinocytes. Ultrastructural immunolocalization studies confine in vivo bound autoantibodies to the cytoplasmic desmosomal plaque. Autoantibody binding studies with the sera of such patients demonstrate that the target antigens are not restricted to squamous epithelia but are also expressed in simple and transitional epithelia, on hepatocytes, and on cells of mesenchymal origin, e.g., myocardial cells. Comparing the clinicopathological features of ten patients with EM major, we could not define any discriminating clinical symptoms among patients with or without autoantibodies. Histopathological examination, however, revealed that only patients with EM major and autoantibodies against dp I and II show suprabasal acantholysis in lesional skin and mucous membranes, suggesting a potential role of the humoral immune response in the pathogenesis of this disease. These findings suggest that these autoantibodies define a subset of patients within the clinical spectrum of EM.

Graft-versus-Host-Like Mucocutaneous Eruptions with Serological Features of Paraneoplastic Pemphigus and Systemic Lupus erythematosus in a Patient with Non-Hodgkin’s Lymphoma

“…Recently, single case reports of overlapping antibody specificities in PNP and pemphigus vulgaris [17] and a case of bullous pemphigoid [27] have given evidence of further overlapping entities. Autoantibodies against desmoplakins I and II, initially thought to be pathognomonic for PNP, have lately also been found to occur under few other conditions: a subgroup of erythema multiforme major [28], PNP without detectable neoplasm (entire complex of antigens detectable) [29] and PNP with autoantibody deposition in bronchial epithelium after autologous bone marrow transplantation [30]. Mechanisms of true GVH disease [1, 2] may have been involved in this case.…”

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus

“…In fact, several reports demonstrate penetration of IgG autoantibody into living cells (19,20). Notably in keratinocytes, by using passive transfer and in vitro cell culture systems, a series of recent investigations have also demonstrated that IgG autoantibodies to desmoplakin I/II, entirely intracellular desmosomal antigens, can get into living cells and reach the target antigens (21)(22)(23). Moreover, anti-nuclear IgG antibodies from patients with systemic lupus erythematosus have been shown to penetrate into living epithelial cells via receptor-mediated endocytosis and subsequently localize to the corresponding intracellular target antigens (24).…”

Lack of a Specific Humoral Autoreactivity in Sera from Patients with Early Erythema Exsudativum Multiforme Majus

“…One reason for the different outcome of our study compared with the initial work (Foedinger et al, 1995(Foedinger et al, , 1996 might be the tight window between diagnosis of the disease and serum sampling in our cohort. This may have reduced the detection of epiphenoma following the preceding tissue destruction due to an extended inflammatory response (Cozzani et al, 2011).…”

“…Infiltrating TO THE EDITOR Erythema exsudativum multiforme majus (EEMM) is a rare condition affecting both skin and mucous membranes. It is assumed that humoral immune reponses may contribute to the pathogenesis of the disease, and the presence of autoantibodies was described in 7 of 10 EEMM patients (Foedinger et al, 1995(Foedinger et al, , 1996. These autoantibodies were associated with desmosomal staining by direct immunofluorescence microscopy of skin and by indirect immunofluorescence tests using monkey esophagus as a substrate, and they produced 210/ 250 kDa bands by immunoblotting of epidermal extracts, and immunoprecipitated proteins of apparently 210/250 kDa from lysates of human keratinocytes.…”