Gabriele Hinterhuber

Paraneoplastic pemphigus in association with hepatocellular carcinoma

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease associated with neoplasms, most frequently of the lymphoproliferative type. Rare PNP cases related to nonhematological solid tumors have been reported. The patient in this report presented with severe mucocutaneous involvement of PNP associated with hepatocellular carcinoma. Histopathology showed vacuolar interface dermatitis with keratinocyte necrosis and intraepidermal acantholysis. Direct immunofluorescence exhibited deposition of intercellular IgG and complement and granular complement at the dermoepidermal junction. Indirect immunofluorescence testing showed a typical intercellular staining on monkey esophagus and rat bladder epithelium. Immunoprecipitation showed characteristic target antigens of 250, 210, and 190 kDa molecular weights. This patient met all diagnostic criteria for paraneoplastic pemphigus and is, to our knowledge, the first report of a case associated with hepatocellular carcinoma.

Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours

Background  In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol‐binding protein.

Systemic activation of coagulation and fibrinolysis during varicose vein stripping

BACKGROUND Elevation of activation markers of blood coagulation (thrombin‐antithrombin complex [TAT], prothrombin fragment 1 + 2 [F1 + 2], D‐Dimer] has not only been found in clinically avert thrombosis but also reflects a prethrombotic state. OBJECTIVE The purpose of our study was to evaluate whether varicose vein stripping, an operative procedure with an extremely low risk of postoperative thromboembolism, induces a prethrombotic state by activation of the hemostatic system. METHODS In a prospective, observational study we compared the baseline and postoperative values of TAT, Fl + 2, and D‐Dimers in 15 patients undergoing varicose vein stripping and in 11 control patients undergoing surgical procedures associated with only minor soft tissue trauma. RESULTS A highly significant postoperative elevation of TAT (P < 0.001), Fl + 2 (P = 0.006), and D‐Dimer (P < 0.001) was observed in the varicose vein stripping group. No significant postoperative change of the respective parameters was detected in the control group. CONCLUSION We therefore conclude that varicose vein stripping induces a significant hemostatic system activation although postoperative thrombotic events are rare.

Enzyme-linked immunosorbent assay for detection of peptide-specific human antidesmoplakin autoantibodies.

Background  Autoantibodies directed against desmoplakin (Dp) I and II have recently been characterized in a subset of patients with severe erythema multiforme (EM), a recurrent inflammatory skin disease with a broad spectrum of clinical manifestations. These autoantibodies recognize a peptide epitope localized within the extreme end of the carboxy terminal domain of Dp responsible for the assembly of keratin filaments to the desmosomal plaque. Using dot blot analysis with overlapping synthetic peptides, the binding epitope YSYSYS has been identified.

Internalization via plasmalemmal vesicles: a route for antidesmoplakin autoantibodies into cultured human keratinocytes

Abstract:  Recently, autoantibodies to desmoplakin I and II have been identified in a subset of patients with a severe form of erythema multiforme. These autoantibodies recognize a specific peptide sequence at the carboxy terminal domain of desmoplakin I and II responsible for interaction with keratin filaments. Desmoplakins are major constitutive proteins of the inner dense desmosomal plaque of keratinocytes and are entirely localized within the cells. With the assumption of pathogenecity for circulating autoantibodies, the question arose how antidesmoplakin autoantibodies enter keratinocytes. Utilizing immunhistochemical procedures for cell motility and time kinetic studies at the light‐ and electron‐microscopic level, we found that autoantibodies are bound at the cell surface of cultured human keratinocytes, internalized via plasmalemmal vesicles, and are found consecutively within tubulo‐vesicular structures inside the cells. At the same time, a fraction of antibodies can be detected at the inner dense desmosomal plaques. Immunogold labeling reveals internalization of autoantibodies in small non‐coated plasmalemmal vesicles positive for caveolin. These observations indicate that vesicular transport may represent a relevant biological mechanism for antidesmoplakin autoantibodies to enter keratinocytes and allow access to their corresponding antigenic target in vivo.