Hiromu Soh

The ratio of lipidperoxides to superoxide dismutase activity in the skin lesions of patients with severe skin diseases: An accurate prognostic indicator

We studied 35 patients with active inflammatory skin diseases, measuring the levels of lipidperoxides and of the oxygen radical scavenging enzyme superoxide dismutase (SOD) in biopsy specimens of skin lesions. Lipidperoxide levels were markedly elevated in all patients. In fifteen patients with disease that was severe and highly resistant to therapy, SOD activity was only slightly increased, in comparison with normal controls. In contrast, in the twenty patients with mild disease that responded well to therapy, SOD activity was markedly elevated. The ratio of lipidperoxide levels to SOD activity was thus an accurate prognostic indicator, being elevated only in the group not responding to treatment. These findings suggest that the severity of allergic inflammatory skin disease and/or the response to treatment may in part be governed by the degree to which the patients SOD activity is up-regulated in response to the generation of tissue-damaging substances such as lipidperoxides. Interestingly, our studies revealed the SOD activities of both normal and inflamed skin to be unexpectedly high; our data suggest that SOD plays a critical role in protecting the skin from the effects of oxygen radicals and ultraviolet light.

IgE and its related phenomena in bullous pemphigoid

This study was designed to analyse IgE and its related phenomena in bullous pemphigoid (BP). We analysed 17 BP sera by indirect immunofluorescenee (IIF) and immunoblotting (IB) using a monoclonal antibody to IgE. In addition, inflammatory cells in lesional skin from 11 patients with BP were analysed by the alkaline phosphatase‐anti‐alkaline phosphatase (APAAP) technique using monoclonal antibodies to IgE and FcɛRII/CD23. IgE class anti‐basement membrane zone (BMZ) autoantibody was detected in nine of 17 sera (52.9%) by IIF. IgG class anti‐BMZ antibody could block the BMZ‐binding reactivity of IgE class antibody. Titres of IgE class autoantibody in the sera ranged from 1:40 to 1:320, and statistically correlated with serum IgF levels. Two of 11 sera contained an IgE class autoantibody which recognized a 230‐kDa BP antigen by IB. By radio‐allergosorbent test (RAST), IgE‐specific antibodies to an extended series of common inhalant and food allergens were detectable in six sera with higb concentrations of total IgF(over 3300 IU/ml). IgE‐bearing and FcɛRII‐expressing cells were demonstrated in the upper dermis and along the BMZ in seven of 11 biopsy specimens by tbe APAAP technique. The distribution and number of IgE‐bearing cells in the lesions were similar to those of the FcEERII‐expressing cells. Tbese results suggest that botb IgE‐mediated immune responses and autoimmunity characterize BP as distinctive features.

The effect of ultraviolet (UVB and PUVA) radiation on the expression of epidermal keratins

Using a panel of monoclonal antibodies directed against keratins (PKK2. CK8.12 and KL1). the effects of ultraviolet B (UVB) and psoralen plus ultraviolet A (PUVA) irradiation on keratin expression in guinea‐pig skin were examined immunohistoehemically. Following irradiation, whether by UVB or PUVA, rapid alterations in the distribution pattern of keratins were observed in the epidermis. The alterations included the induction of basal cell‐type keratins (PKK2 and CK8.12 staining) in the suprabasal layers, with concomitant reduction ofthe suprabasal‐type keratins (KL1 staining). These alterations in keratin expression were observed during the period when DNA synthesis appears to be accelerated by ultraviolet light exposure (5 h–5 days after LIVB, and 2–10 days after PUVA irradiation). Therefore, these changes are probably reflections ofa proliferative or regenerative state of keratinocytes. This explanation was supported by the result of an experiment involving tape stripping of the epidermal horny layers, which also accelerates DNA synthesis hy keratinocytes. Immunohistochemistry appears to be a useful and sensitive method of detecting the effect of ultraviolet light on keratinization.

The distribution of IgG subclass autoantibodies in bullous pemphigoid analysed by immunofluorescence and immunoblotting

SummaryThe distribution of IgG subclasses in bullous pemphigoid (BP) autoantibodies in 14 BP sera and four biopsies was analysed by immunofluorescence (IF) and immunoblotting (IB). Three clones of monoclonal antibodies (MoAbs) to each IgG subclass were used. All 14 sera showed linear fluorescence in the basement membrane zone with IF, and 240 kDa and/or 180 kDa protein bands in human epidermal extract were detected by IB using a polyclonal antibody to total IgG. BP antibody in IgG4 subclass was found to be predominant, as it was detected most frequently and intensively in all positive sera and lesions studied by both techniques. In the IgG1 to IgG3 subclasses, a range of proportions of positive sera was obtained among MoAbs to the same IgG subclass in both techniques. However, one MoAb could detect IgG1 subclass BP antibody with a high frequency in both techniques. No difference in IgG subclass distribution of BP antibodies was observed during the course of the disease. In each serum, any IgG subclass of BP antibody recognized the identical BP antigen(s). These results suggest the predominance of IgG4 subclass and the possible presence of IgG1 subclass in BP antibodies.

Serum Levels of Soluble CD23 in Patients with Bullous Pemphigoid

In this study, we tested the serum levels of soluble CD23 (sCD23) in 27 bullous pemphigoid (BP) patients and compared them with the disease activity. Soluble CD23 is the cleaved portion of the low affinity Fc receptor for IgE (FcɛRII/CD23) which has an affinity for IgE and regulates IgE synthesis. Although bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgG class autoantibodies against the basement membrane of stratified squamous epithelia, several IgE‐related phenomena have been reported. Recently, we have shown that FcɛRII‐expressing and IgE‐bearing cells are detectable in the lesional skin and concluded that an IgE‐FcɛRII/CD23 system may be involved in the pathogenesis of this disease.