Background: Recently, epidermal transglutaminase (TG) has been identified within the papillary IgA granules in dermatitis herpetiformis (DH). Although IgA type autoantibodies to tissue and epidermal TGs are characteri...Background: Recently, epidermal transglutaminase (TG) has been identified within the papillary IgA granules in dermatitis herpetiformis (DH). Although IgA type autoantibodies to tissue and epidermal TGs are characteristic serological markers for DH, these antibodies do not bind to normal papillary skin structures. Aims: To test the possibility of IgA immune com-plex precipitation within the vessel walls as a first step in the pathogenesis of skin symptoms, we analysed immunoglobulin, complement, and epidermal TG deposition along the vascular system of DH skin. Methods: Punch biopsy specimen were taken from 116 DH patients’ skin,and evaluated for the presence of vascular immune precipitates by direct immunofl uorescence. Skin samples from 16 DH patients were also studied for tissue and epidermal TGs. Results: In 74 (64% ) of the 116 DH skin studied, significant vascular staining accompanied the DH-specific granular IgA fluorescence (IgA and C3 in 39 patients; IgA alone in 18; IgA, C3 and IgM together in five; IgM alone in 12). In most cases (92% ), the precipitates were detected in the small vessels of the papillary dermis; however, a subpapillary vascular fluorescence was also observed in a few patients (8% ). Skin IgA colocalized with epidermal TG in the vessel walls and within the scattered papillary peri-and intervascular DH bodies. Tissue TG did not colocalize either with the immunoglobulins or with the complement precipitates of the dermis. Furthermore, we could not detect keratinocyte TG in the DH bodies nor in the vessel walls. Conclusions: These findings support possible immune complex precipitation in the vessel walls of DH skin and further confirm the significance of epidermal but not tissue TG in the pathomechanism of skin symptoms.展开更多
Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immuno...Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.展开更多
文摘Background: Recently, epidermal transglutaminase (TG) has been identified within the papillary IgA granules in dermatitis herpetiformis (DH). Although IgA type autoantibodies to tissue and epidermal TGs are characteristic serological markers for DH, these antibodies do not bind to normal papillary skin structures. Aims: To test the possibility of IgA immune com-plex precipitation within the vessel walls as a first step in the pathogenesis of skin symptoms, we analysed immunoglobulin, complement, and epidermal TG deposition along the vascular system of DH skin. Methods: Punch biopsy specimen were taken from 116 DH patients’ skin,and evaluated for the presence of vascular immune precipitates by direct immunofl uorescence. Skin samples from 16 DH patients were also studied for tissue and epidermal TGs. Results: In 74 (64% ) of the 116 DH skin studied, significant vascular staining accompanied the DH-specific granular IgA fluorescence (IgA and C3 in 39 patients; IgA alone in 18; IgA, C3 and IgM together in five; IgM alone in 12). In most cases (92% ), the precipitates were detected in the small vessels of the papillary dermis; however, a subpapillary vascular fluorescence was also observed in a few patients (8% ). Skin IgA colocalized with epidermal TG in the vessel walls and within the scattered papillary peri-and intervascular DH bodies. Tissue TG did not colocalize either with the immunoglobulins or with the complement precipitates of the dermis. Furthermore, we could not detect keratinocyte TG in the DH bodies nor in the vessel walls. Conclusions: These findings support possible immune complex precipitation in the vessel walls of DH skin and further confirm the significance of epidermal but not tissue TG in the pathomechanism of skin symptoms.
文摘Causative gene defects have not been demonstrated in the majority of nonbullous congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and ultrastructural observations, transglutaminase activity assays and sequencing of TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1 (TGase 1), involucrin and loricrin expression and in situ transglutaminase activity were present in all of the cases. Ultrastructurally, two cases out of five showed incomplete thickening of the cornified cell envelope (CCE) during keratinization and the other three exhibited abnormal lipid droplets in the cornified cells and malformed lamellar granules. No TGM1 mutation was found in any of the four families by direct sequence analysis. NBCIE cases with normal TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal lipid droplets and malformed lamellar granules and the other with defective CCE formation.
