Specific detection of anti-cell surface antibodies in herpes gestationis sera

Abstract We examined 42 herpes gestationis sera with immunofluorescence of normal human skin sections, and found that anti-keratinocyte cell surface antibodies were detected specifically in 10 herpes gestationis sera. The diagnosis of these herpes gestationis cases was confirmed by detecting antibodies against the 180 kD bullous pemphigoid antigen with immunoblotting of its fusion protein. The results of immunoadsorption assay using baculoproteins of both pemphigus vulgaris and pemphigus foliaceus antigens indicated that the herpes gestalionis sera did not recognize common pemphigus antigens. Immunoblotting of human epidermal extracts and immunofluorescence of various tissues also suggested that the sera did not recognize any other desmosomal components or paraneoplastic pemphigus antigens. The significance of this reactivity is unclear. However, because no control bullous pemphigoid sera showed this reactivity, it may suggest a different pathophysiology between herpes gestationis and bullous pemphigoid.     

Immediate hypersensitivity parameters in bullous pemphigoid

Elevated serum IgE levels gave rise to the hypothesis that type 1 immune reaction is implicated in the pathology of Bullous Pemphigoid. IgE serum levels were estimated in 91 patients with Bullous Pemphigoid (BP) and in 26 healthy individuals. In 30 of the patients, the dermal mast cell infiltrate and peripheral blood eosinophils (%) were studied. Patients were subdivided in four groups according in diagnostic criteria or treatment. It was found that all patients, including those receiving treatment, had considerably elevated serum IgE compared to controls. Patients fulfilling all criteria had markedly increased IgE compared to those with negative indirect immunofluorescence. A significant correlation was found between serum IgE and dermal mast cell infiltrate but not between serum IgE and peripheral blood eosinophils, or between peripheral eosinophilia and dermal mast cells. Immediate hypersensitivity parameters, systemic or local, are apparently involved in BP lesion formation although to date it remains unknown at which particular step such parameters might be crucial. The possible biological significance of IgE overproduction and its interrelationship with local inflammatory cellular events is discussed.     

Benign mucous membrane pemphigoid with linear IgA deposits in oral mucosa

Two patients with severe oral ulcerations and concomitant lesions in the nose, eyes and genitals were examined. The immunofluorescence (IFL) studies of buccal and genital mucosa revealed that the only deposited immunoglobulin was IgA. Immunoelectron microscopy confirmed the linear pattern of IgA deposition and localized IgA in lamina lucida in both patients. Dapsone 50 mg daily was effective in controlling the disease activity partially in the first and completely in the second patient. The results suggest that our patients had benign mucous membrane pemphigoid (BMMP) with linear IgA deposition but do not exclude a mucosal form of a newly recognized bullous skin disease termed linear IgA disease.     

Antibody-Binding to the 180-kD Bullous Pemphigoid Antigens at the Lateral Cell Surface Causes Their Internalization and Inhibits Their Assembly at the Basal Cell Surface in Cultured Keratinocytes

We demonstrated the effects of monoclonal antibodies to the 180-kD and 230-kD BP antigens (BPA) and of BP sera on Ca⁺⁺-induced formation of hemidesmosomes in cultured human keratinocytes (a cell line, DJM-1) by immunofluorescence microscopy. Under low Ca⁺⁺ (0.07 mM) conditions, the 180-kD and 230-kD BPAs were distributed homogeneously on the basal plasma membrane, while they formed a peculiar concentric ring or arch (ring/arch) arrangement in high-Ca⁺⁺ (1.87 mM) medium. On the other hand, the apical-lateral cell membrane was stained homogeneously with antibodies to the 180-kD BPA, but not to the 230-kD BPA, both in low and high Ca⁺⁺ media. The low-high Ca⁺⁺ switch at first caused disappearance of the antigen from the basal plasma membrane and then formed the high-Ca⁺⁺ ring/arch pattern within 3 hrs. In this system, monoclonal antibodies to the 180-kD and 230-kD BPAs and the sera from 5 BP patients, 2 pemphigus vulgaris (PV) patients, and 4 normal volunteers were added into the culture media. The addition of anti-180-kD BPA antibodies or any BP serum caused the internalization of the 180-kD BPA from the apical-lateral cell membrane and inhibited the Ca⁺⁺-induced formation of the ring/arch pattern on the basal membrane, possibly by inhibiting the movement of the antigen from the lateral to the basal membrane to form hemidesmosomes. The internalized fluorescence dots were shown to be composed of the 180-kD BPA and patient's IgG, but not of the 230-kD BPA by double-immunostaining, suggesting the internalized 180-kD BPA was from the apical-lateral membrane, but not from hemidesmosomes. Monoclonal antibodies to the 230-kD BPA and normal and PV sera did not cause these effects. These results suggest that autoantibodies to the 180-kD BPA, but not to the 230-kD BPA, may directly bind the antigen on the cell surface and disturb the formation of hemidesmosomes.     

Ocular surface impressions using cellulose acetate filter material. Ocular pemphigoid

A technique for obtaining ocular surface impressions using cellulose acetate filter material is described. A representative ocular surface impression obtained by this technique from a patient with cicatricial ocular pemphigoid is shown, and contrasted to a normal ocular surface impression.     

Bullous pemphigoid antigen concentration in normal human skin in relation to body area and age

Summary The amount of bullous pemphigoid antigen (BPA) in normal human skin on different areas of the body and in bodies of different ages was determined by making endpoint titer estimations using the indirect immunofluorescence technique. Two sera with bullous pemphigoid antibodies were tested with 36 specimens of normal human skin from six cadavers. The greatest expression of BPA was found in plantar sites, whereas the lowest endpoint titers were seen in flexural arm biopsy specimens. Age-dependent differences in BPA expression were detected as well. The oldest individuals tested produced the highest endpoint titers in contrast to the lowest endpoint titers in the youngest. This study suggests that the amount of BPA depends not only on the body region where the biopsy specimen is taken but also on the age of the donor. This is important to know in connection with indirect immunofluorescence assays for BP antibodies on human skin.     

Abnormal fibrous protein isolated from the stratum corneum of a patient with bullous congenital ichthyosiform erythroderma (BCIE)

Summary The fibrous protein of stratum corneum was isolated from a patient with bullous congenital ichthyosiform erythroderma (BCIE), and its properties characterized using electron microscopy, amino acid analysis and SDS gel electophoresis. Results were compared with the characteristics of the fibrous protein isolated from stratum corneum of normal controls.From 900 mg (dry weight) of stratum corneum, 68 mg of fibrous protein was obtained from the patient, while 178 mg was obtained from the normal control. Structural differences were observed with electron microscopy and chemical differences were shown in the ratio of several amino acids. On SDS electrophoresis, the 55,000 dalton constituent of normal fibrous protein could not be identified in the fibrous protein from this patient. These results suggest that an alteration of the polypeptide composition of fibrous protein from this patient with BCIE occurred, and this alteration induced the morphological and clinical features of this dominant genetic keratinization disorder.This study was supported by a research grant for genetic keratinization disorders (H.O.) from the Ministry of Health and Welfare of Japan and by a research grant for biochemical mechanisms of keratinization (H.O.) from Japan Lydia O'Leary Memorial Foundation in 1978     

Disseminated cicatricial pemphigoid in a child and in an adult. Ultrastructural diagnostic criteria and differential diagnosis with special reference to acquired epidermolysis bullosa

Summary The first case of an infant affected with a rare, disseminated variant of benign cicatricial pemphigoid is described, showing the same ultrastructural features of initial blister formation as an adult patient. These consist in edematous changes within the superficial dermis caused by vesiculation or dissolution of cellular and noncellular connective tissue elements, coalescing into subepidermal blisters. Differential diagnosis excludes other nonhereditary bullous disorders because of the ultrastructure of the dermo-epidermal junction in nascent blisters and in perilesional skin. In spite of evident clinical, histological, and immunohistological similarities as well as controversial and confusing immunological studies, acquired epidermolysis bullosa can be clearly separated from our case by a diagnostic hallmark on the electron-microscopical level, i.e., band-like IgG depositions beneath the basal lamina. This is demonstrated in comparing the two cases of disseminated cicatricial pemphigoid with three patients suffering from acquired epidermolysis bullosa, thus providing evidence that disseminated cicatricial pemphigoid and acquired epidermolysis bullosa are two distinct nosologic entities.     

角膜板层烧烙联合羊膜移植治疗大泡性角膜病变

目的:研究角膜板层烧烙联合羊膜移植治疗大泡性角膜病变(bullous keratopathy,BK)的疗效.方法:对12例(12眼)BK患者采用角膜板层烧烙联合羊膜移植治疗,其中绝对期青光眼7例,人工晶状体眼4例,角膜穿孔伤1例.结果:患者12例术后眼部疼痛等刺激症状均消失,随访3～48 mo均未发现BK复发及并发症的发生.结论:角膜板层烧烙联合羊膜移植可有效地控制BK的症状,防止BK的复发,是治疗BK可供选择的有效方法.