OBJECTIVETo investigate the relationship between the levels of antidesmoglein (DSG) 1, 3 antibodies in the sera of patients with paraneoplastic pemphigus (PNP) and alopecia.

METHODSSera from PNP patients, bullous pemphigoid patients, and normal healthy subjects were collected and 2 tissue samples from 2 healthy scalps were resected. Anti-DSG 1, 3 antibodies in the sera of PNP patients were detected by enzyme-linked immunosorbent assay (ELISA). Indirect immunofluorescent assay was used to detect whether the antibodies in the sera of PNP patients binds with the follicular epithelium of normal healthy scalp.

RESULTSAnti-DSG3 autoantibody was strongly positive and anti-DSG1 weakly positive in one patient, while both two antibodies were negative in the other patient. Their sera could bind to keratinocytes and follicular epithelium in human scalp. Immunofluorescent signals were found on the intercellular epidermal cell surface and outer root sheath of the follicular epithelium. However, the immunofluorescent signals in the section incubating with serum of bullous pemphigoid were only found on basal membrane zone. No signals were found in the section incubating with normal healthy serum.

CONCLUSIONAlopecia in PNP patients are correlated with the anti-DSG3.

Adult ; Alopecia ; etiology ; immunology ; Autoantibodies ; blood ; Desmoglein 1 ; immunology ; Desmoglein 3 ; immunology ; Female ; Humans ; Male ; Paraneoplastic Syndromes ; complications ; immunology ; Pemphigus ; complications ; immunology

OBJECTIVETo explore whether the antibody subtypes against the extracellular 1-2 (EC1-2) epitopes of pemphigus vulgaris antigen (PVA) are related to the pathogenesis of PVA.

METHODSEC1-2 fusion protein, emulsified with complete Freund's adjuvant (CFA) or aluminum hydroxide hydrate [Al ( OH)3], was used to immunize C57BL/6 mouse. After immunization, the cytokine types, specific antibody titers, and antibody subtypes were detected. Also, a neonatal mice model was used to evaluate the pathogenesis of different antibodies.

RESULTSTh1 type cytokine interferon gamma (IFNgamma) was elevated in CFA group, while Th 2 type cytokine interleukin-4 (IL-4) was increased in Al (OH)3 group. The antibody subtypes were different in both groups. After the two groups were transferred with antisera separately, the neonatal mice developed erosion on the skin from Al(OH)3 group, with acantholysis histopathologically and bright immuno-fluorescence deposition, which was not seen in CFA group.

CONCLUSIONDifferent antibody subtypes may contribute to the pathogenesis of disease.

Animals ; Antibody Specificity ; Autoantibodies ; immunology ; Desmoglein 3 ; immunology ; Epitopes ; immunology ; Mice ; Mice, Inbred C57BL ; Pemphigus ; immunology ; pathology

BACKGROUND: Desmogleins are transmembrane glycoproteins of the desmosome which provide mechanical strength to epithelial tissue. Desmogleins have so far, been implicated in several diseases such as pemphigus, striate palmoplantar keratoderma, 4S and squamous cell carcinomas. Skin cancer usually occurs in old age. And there are reports that the expression of desmogleins are increased in squamous cell carcinoma. However the role of desmogleins in skin aging has not yet been reported. OBJECTIVE: The purpose of this study was to investigate the expression of desmoglein 1 and 3 according to chronologic skin aging. METHODS: A total of 6 normal tissue samples from sun-protected skin of different age groups (from 34-year-old to an 84-year-old) and 1 squamous cell carcinoma tissue from a 72-year-old patient were taken. Western blotting and immunohistochemical staining were performed with anti desmoglein 1 and 3 antibodies. The expression of desmoglein 1 and 3 by Western blotting were calculated semiquantitatively by a densitometer. RESULTS: The expression of desmoglein 1 was 0.382 in the 34-year-old, 0.450 in the 45-year-old, 0.369 in the 56-year-old, 0.761 in the 65-year-old, 1.035 in the 77-year-old and 1.329 ODu/mm2 in the 84-year-old. The expression of desmoglein 3 was 0.830 in the 34-year-old, 0.984 in the 45-year-old, 1.029 in the 56-year-old, 1.534 in the 65-year-old, 1.714 in the 77-year-old and 1.878 ODu/mm2 in the 84-year-old. In immunohistochemical staining, the expression of Dsg1 increased from the basal layer to the granular layer and Dsg3 was expressed in the basal and suprabasal layers. CONCLUSION: The expression of desmoglein 1 and 3 were increased according to chronologic skin aging.
Adult ; Aged ; Aged, 80 and over ; Antibodies ; Blotting, Western ; Carcinoma, Squamous Cell ; Desmoglein 1* ; Desmoglein 3 ; Desmogleins* ; Desmosomes ; Glycoproteins ; Humans ; Keratoderma, Palmoplantar ; Middle Aged ; Pemphigus ; Skin Aging* ; Skin Neoplasms ; Skin*

During a search for keratinocyte differentiation-related genes, we obtained a cDNA fragment from the 5'-untranslated region of a previously identified splicing variant of desmoglein 3 (Dg3). This transcript encodes a protein of 282 amino acids, which corresponds to the N-terminal truncated intracellular domain of Dg3 (Delta NDg3). Northern blot analysis detected a 4.6-kb transcript matching the predicted size of Delta NDg3 mRNA, and Western blot analysis with an antibody raised against the Dg3 C-terminus (H-145) detected a 31-kDa protein. Increased Delta NDg3 expression was observed in differentiating keratinocytes by RT-PCR and Western blot analysis, suggesting that Delta NDg3 is indeed a differentiation-related gene product. In immunohistochemical studies of normal and pathologic tissues, H-145 antibody detected the protein in the cytoplasm of suprabasal layer cells, whereas an antibody directed against the N-terminal region of Dg3 (AF1720) reacted with a membrane protein in the basal layer. In addition, Delta NDg3 transcript and protein were upregulated in psoriatic epidermis, and protein expression appeared to increase in epidermal tumors including Bowen's disease and squamous cell carcinoma. Moreover, overexpression of Delta NDg3 led to increased migration and weakening of cell adhesion. These results suggest that Delta NDg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin.
Cell Adhesion ; *Cell Differentiation ; Cell Movement ; Cells, Cultured ; Desmoglein 3/*genetics/*metabolism ; Epidermis/cytology ; Gene Expression ; Humans ; Keratinocytes/*cytology ; Skin Diseases/genetics/metabolism ; gamma Catenin/metabolism

Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by vegetating lesions in the inguinal folds and mouth and by the presence of autoantibodies against desmoglein 3. Two clinical subtypes of pemphigus vegetans exist, which are initially characterized by flaccid bullae and erosions (the Neumann subtype) or pustules (the Hallopeau subtype). Both subtypes subsequently develop into hyperpigmented vegetative plaques with pustules and hypertrophic granulation tissue at the periphery of the lesions. Oral administration of corticosteroids alone does not always induce disease remission in patients with pemphigus vegetans. We report here on a 63-year-old woman with pemphigs vegetans. She had a 2-year history of vegetating, papillomatous plaques on the inguinal folds and erosions of the oral mucosa. The enzyme-linked immunosorbent assay was positive for anti-desmoglein 3, but it was negative for anti-desmoglein 1. She was initially treated with systemic steroid, but no improvement was observed. The patient was then successfully treated with a combination of systemic steroid and dapsone with a good clinical response.
Administration, Oral ; Adrenal Cortex Hormones ; Autoantibodies ; Blister ; Dapsone ; Desmoglein 3 ; Enzyme-Linked Immunosorbent Assay ; Female ; Granulation Tissue ; Humans ; Middle Aged ; Mouth ; Mouth Mucosa ; Pemphigus

BACKGROUNDThe presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus (PNP). Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris (PV), has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin (EPL) and periplakin (PPL) are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments.

METHODSWe characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients' sera and their associated tumors by enzyme-linked immunosorbent assay (ELISA) and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes (HEK), to evaluate the changes of cell-cell adhesion.

RESULTSAutoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes.

CONCLUSIONAutoantibodies against EPL and PPL may also be pathogenic in PNP.

Adolescent ; Adult ; Autoantibodies ; immunology ; pharmacology ; Cell Adhesion ; drug effects ; Cells, Cultured ; Desmoglein 3 ; immunology ; Enzyme-Linked Immunosorbent Assay ; Epidermis ; cytology ; Female ; Humans ; Keratinocytes ; cytology ; drug effects ; Male ; Membrane Proteins ; immunology ; Middle Aged ; Paraneoplastic Syndromes ; immunology ; metabolism ; Pemphigus ; immunology ; metabolism ; Plakins ; immunology ; Protein Precursors ; immunology ; Young Adult