Bullous Pemphigoid, Herpes Gestationis and Linear Dermatitis Herpetiformis: Circulating Anti-Basement Membrane Zone Antibodies; in Vitro Studies

It is well established that suprabasal acantholysis can be produced in tissue culture of normal human skin in the presence of pemphigus IgG autoantibody. In this study, bullous pemphigoid, herpes gestationis and linear dermatitis herpetiformis anti-basement membrane zone antibodies failed to produce dermoepidermal separation in a tissue culture model in spite of the presence of complement. The binding of the antibodies was demonstrated by immunofluorescence and immunoelectron microscopy; ultrastructurally, identical binding sites of anti-basement membrane zone antibodies could be demonstrated in vitro, as has been observed in vivo previously. Tissue culture is a suitable model for studying the binding sites of circulating anti-basement membrane zone antibodies but the functional activity (blister formation) of these antibodies cannot be assessed thereby

Detection of a Specific Inhibitor of Interleukin 1 in Sera of UVB-Treated Mice

It was recently demonstrated that murine keratinocytes upon irradiation with ultraviolet (UV) light release an immunosuppressive cytokine which blocks the biological activity of interleukin 1 (IL 1). This epidermal cell derived inhibitor (EC-contra IL 1) exhibits a molecular weight of 40 kD and a pI of approximately 9.0. EC-contra IL 1 in vivo possibly may penetrate through the basal lamina and subsequently cause systemic immunosuppression following UV-exposure. In the present study, we tested whether EC-contra IL 1 can also be detected in vivo. Serum samples obtained from total body UV-exposed mice were subjected to HPLC gel filtration and tested for IL 1 inhibitory activity. While a non-specific high molecular weight (300 kD) suppressor factor was detected in sera of both UV-exposed and sham treated control mice, a specific IL 1 inhibitor exhibiting a molecular weight of 40 kD was observed only in sera of UV-exposed mice. This cytokine named serum-contra IL 1 was maximally released 24 h after UV-exposure, exhibited a pI of 9.0, and blocked the activity of natural as well as recombinant interleukin 1 in a dose dependent manner. Serum-contra IL 1 did not suppress interleukin 2 or interleukin 3 and did not inhibit spontaneous cell proliferation. The present biochemical and biologic data suggest that serum-contra IL 1 and EC-contra IL 1 appear to be closely related if not identical. These observations therefore indicate that keratinocytes upon UV-irradiation in vivo release EC-contra IL 1 which may at least partly be responsible for the immunosuppression following UV-exposure

Prospective, Randomized, Multicenter, Double-Blind Placebo-Controlled Trial Comparing Adjuvant Interferon Alfa and Isotretinoin With Interferon Alfa Alone in Stage IIA and IIB Melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

PURPOSE: The combination of interferon alfa (IFN{alpha}) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFN{alpha} alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFN{alpha} and isotretinoin compared with IFN{alpha} alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB. PATIENTS AND METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFN{alpha} and isotretinoin (isotretinoin group; 206 patients) or IFN{alpha} and placebo (placebo group; 201 patients) after excision of the primary tumor. IFN{alpha} was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients ≤ 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months. RESULTS: A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility. CONCLUSION: The addition of isotretinoin to an adjuvant treatment of low-dose IFN{alpha} in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended