The Experts below are selected from a list of 1848 Experts worldwide ranked by ideXlab platform
Werner W. Franke - One of the best experts on this subject based on the ideXlab platform.
-
Patterns of Desmocollin synthesis in human epithelia: Immunolocalization of Desmocollins 1 and 3 in special epithelia and in cultured cells
European journal of cell biology, 1996Co-Authors: Ulrike Nuber, Stephan Schafer, Sabine Stehr, Hans Richard Rackwitz, Werner W. FrankeAbstract:Murine monoclonal antibodies (mAbs) which specifically react, in immunoblot and immunolocalization experiments, with the human desmosomal cadherins, Desmocollins Dsc1 (mAb Dsc1-U100) and Dsc3 (mAb Dsc3-U114), have allowed to study systematically the synthesis of these proteins in tissues and cultured cells. Application of these mAbs in immunofluorescence microscopy on human skin has shown the presence of Dsc1 in the suprabasal layers of interfollicular epidermis and a specific cell layer of the hair follicle root sheath, whereas Dsc3 has been identified in all living epidermal layers as well as in glandular ducts and in basal matrix cells and the outer root sheath of hair follicles. Dsc3, but not Dsc1, it also present in desmosomes of the basal as well as suprabasal cell layers of other stratified epithelia such as vagina, tongue and esophagus as well as in cells of the basal layer of bladder urothelium and the complex epithelium of trachea. All the diverse one-layered ("simple") epithelia examined were as negative for both, Dsc1 and Dsc3, as were the non-epithelial desmosomes of the intercalated disks of the myocardium. A special situation has been discovered in the thymus. Here the usually single-layered cells of the thymic reticular epithelium are connected by Dsc3-possessing desmosomes, as they also contain typical (type I) hemidesmosomes, whereas Dsc1 is only detected in the "Hassall bodies", spheroidal formations of densely packed reticulum-derived cells which also produce cytokeratins 1 and 10, indicative of suprabasal epidermal differentiation. In cell cultures most, probably all, desmosomes of diverse cell lines derived from stratified squamous epithelia or squamous cell carcinomas, including primary keratinocytes, HaCaT keratinocytes and A-431 carcinoma cells, contain Dsc3. By contrast, Dsc1 has only been detected in local piles of keratinocytes that appear to be in the process of suprabasal differentiation. The antibodies have also allowed to demonstrate that desmosomes of cell lines can contain more than one Desmocollin isoform. The observations made by immunofluorescence microscopy are compared with results obtained by in situ hybridization of mRNAs, and the potential value of these mAbs in histology and pathology is discussed.
-
Identification of amino acid sequence motifs in Desmocollin, a desmosomal glycoprotein, that are required for plakoglobin binding and plaque formation.
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Sergey M. Troyanovsky, Regina B. Troyanovsky, Leonid Eshkind, Rudolf E. Leube, Werner W. FrankeAbstract:By transfecting epithelial cells with gene constructs encoding chimeric proteins of the transmembrane part of the gap junction protein connexin 32 in combination with various segments of the cytoplasmic part of the desmosomal cadherin Desmocollin 1a, we have determined that a relatively short sequence element is necessary for the formation of desmosome-like plaques and for the specific anchorage of bundles of intermediate-sized filaments (IFs). Deletion of as little as the carboxyl-terminal 37 aa resulted in a lack of IF anchorage and binding of the plaque protein plakoglobin, as shown by immunolocalization and immunoprecipitation experiments. In addition, we show that the sequence requirements for the recruitment of desmoplakin, another desmosomal plaque protein, differ and that a short (10 aa) segment of the Desmocollin 1a tail, located close to the plasma membrane, is also required for the binding of plakoglobin, as well as of desmoplakin, and also for IF anchorage. The importance of the carboxyl-terminal domain, homologous in diverse types of cadherins, is emphasized, as it must harbor, in a mutually exclusive pattern, the information for assembly of the IF-anchoring desmosomal plaque in Desmocollins and for formation of the alpha-/beta-catenin- and vinculin-containing, actin filament-anchoring plaque in E- and N-cadherin.
-
Differential synthesis of type 1 and type 2 Desmocollin mRNAs in human stratified epithelia.
The International journal of developmental biology, 1993Co-Authors: D. G. Theis, Peter J. Koch, Werner W. FrankeAbstract:Epithelial cells are tightly connected by various kinds of junctions, of which the desmosomes (maculae adhaerentes) are particularly prominent. The desmosomes are characterized by two subgroups of constitutive transmembrane glycoproteins, the desmogleins and the Desmocollins, which have been identified as specific members of the larger multigene family of CAMs of the cadherin category. Following our recent observation in bovine tissues that different desmoglein and Desmocollin genes can be expressed in different cell types (Koch, P.J. et al., Proc. Natl. Acad. Sci. USA 89:353-357, 1992), we have now isolated cDNAs encoding human Desmocollins type 1 and type 2. The complete sequence of human type 1 Desmocollin has been determined and identified by its homology to the corresponding bovine gene product. Using in situ hybridization on sections through frozen human tissues, we show that mRNAs for type 2 Desmocollin are synthesized in various stratified epithelia such as epidermis, esophagus and exocervix, whereas type 1 Desmocollin was detected in appreciable amounts only in epidermis. In addition, a striking difference has been observed within the epidermis, where type 2 Desmocollin mRNA can be detected in several basal layers of living cells but type 1 Desmocollin mRNA is restricted to suprabasal layers. The possible functional involvement of Desmocollins in the differentiation of stratified tissues is discussed and the potential value of molecular probes for desmosomal cadherins in tumor diagnosis is emphasized.
-
amino acid sequence of bovine muzzle epithelial Desmocollin derived from cloned cdna a novel subtype of desmosomal cadherins
Differentiation, 1991Co-Authors: Peter J. Koch, Michaela D. Goldschmidt, Michael J. Walsh, Ralf Zimbelmann, Monika Schmelz, Werner W. FrankeAbstract:Abstract Desmosomes are cell-type-specific intercellular junctions found in epithelium, myocardium and certain other tissues. They consist of assemblies of molecules involved in the adhesion of specific cell types and in the anchorage of cell-type-specific cytoskeletal elements, the intermediate-size filaments, to the plasma membrane. To explore the individual desmosomal components and their functions we have isolated DNA clones encoding the desmosomal glycoprotein, Desmocollin, using antibodies and a cDNA expression library from bovine muzzle epithelium. The cDNA-deduced amino-acid sequence of Desmocollin (presently we cannot decide to which of the two Desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a single candidate sequence of 24 amino acids sufficiently long for a trans-membrane arrangement, and an extracellular aminoterminal portion of 561 amino acid residues, compared to a cytoplasmic part of only 176 amino acids. Amino acid sequence comparisons have revealed that Desmocollin is highly homologous to members of the eadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific eadherin. Using riboprobes derived from cDNAs for Northern-blot analyses, we have identified an mRNA of approximately 6 kb in stratified epithelia such as muzzle epithelium and tongue mucosa but not in two epithelial cell culture lines containing desmosomes and desmoplakins. The difference may indicate drastic differences in mRNA concentration or the existence of cell-typespecific Desmocollin subforms. The molecular topology of Desmocollin(s) is discussed in relation to possible functions of the individual molecular domains.
-
Amino acid sequence of bovine muzzle epithelial Desmocollin derived from cloned cDNA: A novel subtype of desmosomal cadherins
Differentiation; research in biological diversity, 1991Co-Authors: Peter J. Koch, Michaela D. Goldschmidt, Michael J. Walsh, Ralf Zimbelmann, Monika Schmelz, Werner W. FrankeAbstract:Desmosomes are cell-type-specific intercellular junctions found in epithelium, myocardium and certain other tissues. They consist of assemblies of molecules involved in the adhesion of specific cell types and in the anchorage of cell-type-specific cytoskeletal elements, the intermediate-size filaments, to the plasma membrane. To explore the individual desmosomal components and their functions we have isolated DNA clones encoding the desmosomal glycoprotein, Desmocollin, using antibodies and a cDNA expression library from bovine muzzle epithelium. The cDNA-deduced amino-acid sequence of Desmocollin (presently we cannot decide to which of the two Desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a single candidate sequence of 24 amino acids sufficiently long for a transmembrane arrangement, and an extracellular aminoterminal portion of 561 amino acid residues, compared to a cytoplasmic part of only 176 amino acids. Amino acid sequence comparisons have revealed that Desmocollin is highly homologous to members of the cadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific cadherin. Using riboprobes derived from cDNAs for Northern-blot analyses, we have identified an mRNA of approximately 6 kb in stratified epithelia such as muzzle epithelium and tongue mucosa but not in two epithelial cell culture lines containing desmosomes and desmoplakins. The difference may indicate drastic differences in mRNA concentration or the existence of cell-type-specific Desmocollin subforms. The molecular topology of Desmocollin(s) is discussed in relation to possible functions of the individual molecular domains.
David R. Garrod - One of the best experts on this subject based on the ideXlab platform.
-
Changing pattern of Desmocollin 3 expression accompanies epidermal organisation during skin development
Developmental dynamics : an official publication of the American Association of Anatomists, 1997Co-Authors: Martyn A.j. Chidgey, Kevin K.m. Yue, Sarah Gould, Carolyn Byrne, David R. GarrodAbstract:The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, Desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the Desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine Desmocollins and examined the induction patterns of Desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the Desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, Desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of Desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of Desmocollin 1 to Desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.
-
distinct Desmocollin isoforms occur in the same desmosomes and show reciprocally graded distributions in bovine nasal epidermis
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Alison J North, Martyn Chidgey, Jonathan P Clarke, William G Bardsley, David R. GarrodAbstract:Abstract The adhesive core of the desmosome is composed of cadherin-like glycoproteins of two families, Desmocollins and desmogleins. Three isoforms of each are expressed in a tissue-specific and developmentally regulated pattern. In bovine nasal epidermis, the three Desmocollin (Dsc) isoforms are expressed in overlapping domains; Dsc3 expression is strongest in the basal layer, while Dsc2 and Dsc1 are strongly expressed in the suprabasal layers. Herein we have investigated whether different isoforms are assembled into the same or distinct desmosomes by performing double immunogold labeling using isoform-specific antibodies directed against Dsc1 and Dsc3. The results show that individual desmosomes harbor both isoforms in regions where their expression territories overlap. Quantification showed that the ratio of the proteins in each desmosome altered gradually from basal to immediately suprabasal and upper suprabasal layers, labeling for Dsc1 increasing and Dsc3 decreasing. Thus desmosomes are constantly modified as cells move up the epidermis, with continuing turnover of the desmosomal glycoproteins. Statistical analysis of the quantitative data showed a possible relationship between the distributions of the two isoforms. This gradual change in desmosomal composition may constitute a vertical adhesive gradient within the epidermis, having important consequences for cell positioning and differentiation.
-
Expression of Full-Length Desmosomal Glycoproteins (Desmocollins) Is Not Sufficient to Confer Strong Adhesion on Transfected L929 Cells
The Journal of investigative dermatology, 1996Co-Authors: Martyn A.j. Chidgey, Jonathan P Clarke, David R. GarrodAbstract:Desmocollins are cadherin-like glycoproteins that are localized in desmosomes. They are thought to play a role in cell adhesion but direct evidence for this is currently unavailable. For this reason we have expressed cDNAs encoding full-length bovine Desmocollin type la and type lb in mouse fibroblast (L929) cells. This system has previously been used to demonstrate the adhesive properties of E-cadherin. E-cadherin-mediated cell-cell adhesion is thought to require interaction of the cytoplasmic domain with the catenins that are expressed in L-cells. Because L929 cells do not express cytoplasmic desmosomal components that may be required for Desmocollin-mediated adhesion, we constructed a chimeric cDNA encoding the bovine type 1 extracellular domain linked to the mouse E-cadherin transmembrane and cytoplasmic domains. cDNAs were transfected into cells and clones that expressed heterologous protein at the cell surface were isolated. The full-length Desmocollins apparently did not interact with any other molecules, but the chimeric protein did bind to endogenous mouse α - and β -catenin. Surprisingly none of the Desmocollin-transfected cell lines showed significant adhesive properties under conditions where cells transfected with E-cadherin exhibited strong adhesiveness. We conclude that Desmocollin expression alone is not sufficient to confer adhesion on transfected cells and more than one desmosomal component may be required.
-
Characterisation of a Desmocollin isoform (bovine DSC3) exclusively expressed in lower layers of stratified epithelia
Journal of Cell Science, 1995Co-Authors: Kevin K.m. Yue, Martyn Chidgey, Takashi Hashimoto, J. P. Clarke, J. L. Holton, J. L. M. Hyam, David R. GarrodAbstract:Desmocollins are cadherin-like glycoproteins involved in cell adhesion and plaque formation in desmosome junctions. Three distinct isoforms, the products of different genes, have been found in bovine tissues. We have reported previously that one of these, DSC3, is expressed only in basal and lower suprabasal layers of stratified epithelia. Using RT-PCR we have now obtained the complete cDNA coding sequence of mature bovine DSC3. It has alternatively spliced ‘a’ and ‘b’ forms found in other Desmocollins but is unique in having a 43 instead of a 46 base pair exon. We have characterised a monoclonal antibody, 07–4G, which is specific for the Dsc3 protein, recognising an epitope in the extracellular domain. Immunofluorescent staining with 07–4G confirms that this isoform is found only in stratified epithelia, being strongly expressed in the basal cell layers of these tissues. The intensity of expression fades gradually in the suprabasal layers and disappears completely below the upper limit of desmosome expression. These results suggest that Dsc3 plays an important role in cell epithelial differentiation.
-
Regulation of Desmocollin transcription in mouse preimplantation embryos
Development, 1995Co-Authors: Jane E Collins, Jo E Lorimer, David R. Garrod, Roger S. Buxton, Sara C. Pidsley, Tom P FlemingAbstract:The molecular mechanisms regulating the biogenesis of the first desmosomes to form during mouse embryogenesis have been studied. A sensitive modification of a reverse transcriptase-cDNA amplification procedure has been used to detect transcripts of the desmosomal adhesive cadherin, Desmocollin. Sequencing of cDNA amplification products confirmed that two splice variants, a and b, of the DSC2 gene are transcribed coordinately. Transcripts were identified in unfertilized eggs and cumulus cells and in cleavage stages up to the early 8-cell stage, were never detected in compact 8-cell embryos, but were evident again either from the 16-cell morula or very early blastocyst (approx 32-cells) stages onwards. These two phases of transcript detection indicate DSC2 is encoded by maternal and embryonic genomes. Previously, we have shown that Desmocollin protein synthesis is undetectable in eggs and cleavage stages but initiates at the early blastocyst stage when Desmocollin localises at, and appears to regulate assembly of, nascent desmosomes that form in the trophectoderm but not in the inner cell mass (Fleming, T. P., Garrod, D. R. and Elsmore, A. J. (1991), Development 112, 527–539). Maternal DSC2 mRNA is therefore not translated and presumably is inherited by blastomeres before complete degradation. Our results suggest, however, that initiation of embryonic DSC2 transcription regulates Desmocollin protein expression and thereby desmosome formation. Moreover, data from blastocyst single cell analyses suggest that embryonic DSC2 transcription is specific to the trophectoderm lineage. Inhibition of E-cadherin-mediated cell-cell adhesion did not influence the timing of DSC2 embryonic transcription and protein expression. However, isolation and culture of inner cell masses induced an increase in the amount of DSC2 mRNA and protein detected. Taken together, these results suggest that the presence of a contact-free cell surface activates DSC2 transcription in the mouse early embryo.
Peter J. Koch - One of the best experts on this subject based on the ideXlab platform.
-
Plakoglobin as a Regulator of Desmocollin Gene Expression
Journal of Investigative Dermatology, 2013Co-Authors: Etienne Tokonzaba, Jiangli Chen, Eliane J. Műller, Radhika Ganeshan, Xing Cheng, Peter J. KochAbstract:Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages, and the heart. The goal of this study was to investigate how Desmocollins (DSCs), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with lymphoid enhancer-binding factor 1 (Lef-1) differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NF-κB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-κB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-κB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for the invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation.
-
Desmocollin 3 is required for pre-implantation development of the mouse embryo.
Journal of cell science, 2006Co-Authors: Zhining Den, Xing Cheng, Maria Merched-sauvage, Peter J. KochAbstract:Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin family of cell adhesion receptors. Together with desmoglein(s), it forms the transmembrane core of desmosomes, a multiprotein complex involved in cell adhesion, organization of the cytoskeleton, cell sorting and cell signaling. Previous reports have suggested that Dsc3 synthesis is largely restricted to stratified epithelia, and that it plays a role in the proper differentiation of these tissues during mammalian embryonic development. To test these hypotheses, we generated Dsc3-null mice. Unexpectedly, homozygous mutants show a pre-implantation lethal phenotype. In fact, most mutants die even before mature desmosomes are formed in the embryo, suggesting a new and unexpected role of Dsc3 during early development.
-
the widespread human Desmocollin dsc2 and tissue specific patterns of synthesis of various Desmocollin subtypes
European Journal of Cell Biology, 1995Co-Authors: Ulrike Nuber, Ansgar Schmidt, Stephan Schafer, Peter J. KochAbstract:By comparison of the cDNA-derived amino acid sequences and the cell type-specific patterns of synthesis we have identified Desmocollin Dsc2 as the most widespread, perhaps ubiquitous Desmocollin subtype. Using Northern blot analyses and ribonuclease protection assays we have found an approximately 5.6 kb mRNA encoding Dsc2 in all the diverse human tissues, tumors and cell lines examined that are known to possess desmosomes, i.e. not only epithelial cells but also myocardiac cells and lymph nodes. By contrast, Desmocollin subtypes Dsc1 and Dsc3 have been detected only in certain stratified squamous epithelia, with the most conspicuous restriction of Dsc1 to epidermis and--remarkably, but unexplained--lymph nodes, and in certain carcinomas and cell lines derived therefrom. We have also determined that both Dsc2 mRNA splice forms, the one encoding the larger polypeptide a and the one coding for the shorter Dsc2b, occur in all the diverse tissues and cell lines examined. We also show that certain cells such as the epidermal keratinocyte line HaCaT and the vulvar carcinoma-derived line A-431 continually synthesize more than one Dsc subtype. The cell type-specific patterns of synthesis of the various Dsg and Dsc subtypes are discussed in relation to tissue development during embryogenesis and to malignant transformations, and the utilization of reagents for the specific Dsg and Dsc subtypes in tumor diagnosis is proposed.
-
Differential synthesis of type 1 and type 2 Desmocollin mRNAs in human stratified epithelia.
The International journal of developmental biology, 1993Co-Authors: D. G. Theis, Peter J. Koch, Werner W. FrankeAbstract:Epithelial cells are tightly connected by various kinds of junctions, of which the desmosomes (maculae adhaerentes) are particularly prominent. The desmosomes are characterized by two subgroups of constitutive transmembrane glycoproteins, the desmogleins and the Desmocollins, which have been identified as specific members of the larger multigene family of CAMs of the cadherin category. Following our recent observation in bovine tissues that different desmoglein and Desmocollin genes can be expressed in different cell types (Koch, P.J. et al., Proc. Natl. Acad. Sci. USA 89:353-357, 1992), we have now isolated cDNAs encoding human Desmocollins type 1 and type 2. The complete sequence of human type 1 Desmocollin has been determined and identified by its homology to the corresponding bovine gene product. Using in situ hybridization on sections through frozen human tissues, we show that mRNAs for type 2 Desmocollin are synthesized in various stratified epithelia such as epidermis, esophagus and exocervix, whereas type 1 Desmocollin was detected in appreciable amounts only in epidermis. In addition, a striking difference has been observed within the epidermis, where type 2 Desmocollin mRNA can be detected in several basal layers of living cells but type 1 Desmocollin mRNA is restricted to suprabasal layers. The possible functional involvement of Desmocollins in the differentiation of stratified tissues is discussed and the potential value of molecular probes for desmosomal cadherins in tumor diagnosis is emphasized.
-
amino acid sequence of bovine muzzle epithelial Desmocollin derived from cloned cdna a novel subtype of desmosomal cadherins
Differentiation, 1991Co-Authors: Peter J. Koch, Michaela D. Goldschmidt, Michael J. Walsh, Ralf Zimbelmann, Monika Schmelz, Werner W. FrankeAbstract:Abstract Desmosomes are cell-type-specific intercellular junctions found in epithelium, myocardium and certain other tissues. They consist of assemblies of molecules involved in the adhesion of specific cell types and in the anchorage of cell-type-specific cytoskeletal elements, the intermediate-size filaments, to the plasma membrane. To explore the individual desmosomal components and their functions we have isolated DNA clones encoding the desmosomal glycoprotein, Desmocollin, using antibodies and a cDNA expression library from bovine muzzle epithelium. The cDNA-deduced amino-acid sequence of Desmocollin (presently we cannot decide to which of the two Desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a single candidate sequence of 24 amino acids sufficiently long for a trans-membrane arrangement, and an extracellular aminoterminal portion of 561 amino acid residues, compared to a cytoplasmic part of only 176 amino acids. Amino acid sequence comparisons have revealed that Desmocollin is highly homologous to members of the eadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific eadherin. Using riboprobes derived from cDNAs for Northern-blot analyses, we have identified an mRNA of approximately 6 kb in stratified epithelia such as muzzle epithelium and tongue mucosa but not in two epithelial cell culture lines containing desmosomes and desmoplakins. The difference may indicate drastic differences in mRNA concentration or the existence of cell-typespecific Desmocollin subforms. The molecular topology of Desmocollin(s) is discussed in relation to possible functions of the individual molecular domains.
T Hashimoto - One of the best experts on this subject based on the ideXlab platform.
-
subcorneal pustular dermatosis type iga pemphigus with autoantibodies to Desmocollins 1 2 and 3
Archives of Dermatology, 2009Co-Authors: Imke Duker, Christian Rose, T Hashimoto, Detlef Zillikens, Jörg Schaller, Johannes KunzeAbstract:Background IgA pemphigus is a rare neutrophilic acantholytic autoimmune disease that is characterized by IgA deposits on keratinocyte cell surfaces. Clinically and histologically, IgA pemphigus is divided into 2 major subtypes: subcorneal pustular dermatosis and intraepidermal neutrophilic IgA dermatosis. We report the first case of subcorneal pustular dermatosis–type IgA pemphigus that showed reactivity to all 3 isoforms of the Desmocollin family by indirect immunofluorescence microscopy of COS7 cells transfected with Desmocollin 1, 2, or 3. Observations We describe a 94-year-old woman with IgA pemphigus with a unique immunopathologic pattern. Direct immunofluorescence microscopy revealed IgA deposits throughout the entire epidermis, with stronger staining in the upper epidermis. The autoantibodies from this patient did not show IgA or IgG reactivity with desmogleins via immunoblotting or enzyme-linked immunosorbent assay. By indirect immunofluorescence by the use of COS7 cells transfected with Desmocollin 1, 2, or 3, IgA autoantibodies in a serum sample from our patient clearly reacted with all of them. Conclusions The pathophysiology and autoantigen profile of bullous autoimmune diseases, especially pemphigus and its subforms, are more complex than previously believed. Because pemphigus seems to be a heterogeneous disorder, further studies are needed to evaluate the complexity of the disease.
-
subcorneal pustular dermatosis type of iga pemphigus demonstration of autoantibodies to Desmocollin 1 and clinical review
British Journal of Dermatology, 2000Co-Authors: H Yasuda, Hitoshi Kobayashi, M. Yamane, T Hashimoto, K Itoh, J NakamuraAbstract:We describe a 40-year-old Japanese man with a 3-year history of vesiculopustular lesions resembling subcorneal pustular dermatosis. Histopathology showed subcorneal pustules containing a few acantholytic cells, and direct immunofluorescence disclosed IgA deposition in the intercellular space of the upper epidermis. Circulating IgA autoantibodies of very low titre were also demonstrated by indirect immunofluorescence. A novel cDNA transfection technique clearly detected IgA autoantibodies reactive with human Desmocollin-1. Combined therapy with dapsone and etretinate improved the skin lesions. We review the clinical features of 49 patients in the literature who presented with vesiculopustular lesions and intraepidermal IgA deposition.
-
Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of autoantibodies to Desmocollin‐1 and clinical review
British Journal of Dermatology, 2000Co-Authors: H Yasuda, Hitoshi Kobayashi, M. Yamane, T Hashimoto, K Itoh, J NakamuraAbstract:We describe a 40-year-old Japanese man with a 3-year history of vesiculopustular lesions resembling subcorneal pustular dermatosis. Histopathology showed subcorneal pustules containing a few acantholytic cells, and direct immunofluorescence disclosed IgA deposition in the intercellular space of the upper epidermis. Circulating IgA autoantibodies of very low titre were also demonstrated by indirect immunofluorescence. A novel cDNA transfection technique clearly detected IgA autoantibodies reactive with human Desmocollin-1. Combined therapy with dapsone and etretinate improved the skin lesions. We review the clinical features of 49 patients in the literature who presented with vesiculopustular lesions and intraepidermal IgA deposition.
-
Unusual acantholytic bullous dermatosis associated with neoplasia and IgG and IgA antibodies against bovine Desmocollins I and II.
Journal of the American Academy of Dermatology, 1994Co-Authors: T P Chorzelski, T Hashimoto, T Nishikawa, T Ebihara, M Dmochowski, M Ismail, S JabłońskaAbstract:There are unusual cases of pemphigus that have antibodies nonreactive with either pemphigus vulgaris or pemphigus foliaceus antigens. We describe a patient with an acantholytic bullous dermatosis and lung cancer with intercellular IgG and IgA antibodies that differed in specificity from those of pemphigus vulgaris and pemphigus foliaceus and reacted with bovine Desmocollins I and II and recombinant Desmocollin protein.
-
Two different isoforms of Desmocollin are recognized by autoantibodies in various types of pemphigus.
Dermatology (Basel Switzerland), 1994Co-Authors: T Hashimoto, T Ebihara, T NishikawaAbstract:We have previously reported that, in addition to well-known pemphigus antigens (desmoglein and pemphigus vulgaris antigen), Desmocollin (Dsc), another desmosomal cadherin, is recognized by certain pemphigus sera. Furthermore, we noticed that two Dsc species with a slightly different relative molecular weight were recognized by various pemphigus sera. This difference may contribute to the different clinicopathological features between the subcorneal pustular dermatosis type and the intraepidermal neutrophilic IgA dermatosis type of intercellular IgA vesiculopustular dermatosis.
Takashi Hashimoto - One of the best experts on this subject based on the ideXlab platform.
-
nonclassical pemphigus with exclusively igg anti Desmocollin 3 specific antibodies
Australasian Journal of Dermatology, 2019Co-Authors: Pilar Iranzo, Takashi Hashimoto, Norito Ishii, Merce AlsinagibertAbstract:We describe a patient with nonclassical clinical and histopathological features of pemphigus with exclusively IgG antibodies against Desmocollin (Dsc) 3 detected by enzyme-linked immunosorbent assay of recombinant eukaryotic protein of Dsc1-Dsc3. The absence of antibodies against other known targets, such as desmogleins, reinforces the role of anti-Dsc antibodies in the pathophysiology of atypical pemphigus.
-
Nonclassical pemphigus with exclusively IgG anti‐Desmocollin 3‐specific antibodies
The Australasian journal of dermatology, 2019Co-Authors: Pilar Iranzo, Takashi Hashimoto, Norito Ishii, Mercè Alsina-gibertAbstract:We describe a patient with nonclassical clinical and histopathological features of pemphigus with exclusively IgG antibodies against Desmocollin (Dsc) 3 detected by enzyme-linked immunosorbent assay of recombinant eukaryotic protein of Dsc1-Dsc3. The absence of antibodies against other known targets, such as desmogleins, reinforces the role of anti-Dsc antibodies in the pathophysiology of atypical pemphigus.
-
Childhood Pemphigus Foliaceus with Exclusive Immunoglobulin G Autoantibodies to Desmocollins.
Pediatric dermatology, 2016Co-Authors: Shamir Geller, Takashi Hashimoto, Andrea Gat, Avikam Harel, Jacob Mashiah, Tal Zeeli, Rüdiger Eming, Norito Ishii, Michael Hertl, Eli SprecherAbstract:Pemphigus refers to a group of potentially fatal blistering skin diseases that are often due to the deleterious effects of autoantibodies directed against desmosomal antigens. Although desmogleins have been mainly implicated as autoantigens in pemphigus, a steadily growing body of evidence suggests that other desmosomal proteins may be causally involved as well. Antibodies directed against Desmocollin-3 have been shown to play a direct role in the pathogenesis of several types of pemphigus. Here we describe the case of a child with localized pemphigus foliaceus and immunoglobulin G (IgG) reactivity exclusively directed to Desmocollins. The present report suggests that autoantibodies against nondesmoglein antigens may play a role in the pathogenesis of superficial pemphigus, in addition to pemphigus vulgaris, paraneoplastic pemphigus, and IgA pemphigus.
-
Short Communication Autoimmunity to Desmocollin 3 in Pemphigus
2015Co-Authors: Xuming Mao, Takashi Hashimoto, Masayuki Amagai, Norito Ishii, Arielle R. Nagler, Sara A. Farber, Eun Jung Choi, Lauren H. Jackson, Kristin M. Leiferman, John J. ZoneAbstract:Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion pro-tein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blister-ing in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of Desmocollin 3, the other major desmosomal cadherin isoform ex-pressed in the basal epidermis, develop suprabasal blisters in skin that are histologically identical to those observed in pemphigus vulgaris, suggesting that Desmocollin 3 might be a target of autoantibodies in some pemphigus vulgaris patients. We now dem-onstrate that Desmocollin 3 is an autoantigen in pem-phigus vulgaris, illustrated in a patient with mucosal
-
Atypical pemphigus with immunoglobulin G autoantibodies against desmoglein 3 and Desmocollin 3.
The Journal of dermatology, 2015Co-Authors: Koji Kamiya, Takashi Hashimoto, Norito Ishii, Kwesi Teye, Yumi Aoyama, Chie Wakashima, Tomoko Kudo, Kimiko Nakajima, Shigetoshi Sano, Keiji IwatsukiAbstract:In patients with pemphigus vulgaris (PV), pathogenic immunoglobulin (Ig)G antibodies are most commonly directed against desmoglein 3 (Dsg3). It has recently been reported, however, that IgG anti-Desmocollin 3 (Dsc3) antibodies are detected in some cases of pemphigus with or without IgG anti-Dsg3 antibodies. We present a case of pemphigus with IgG antibodies against Dsg3 and Dsc3. Subsequent studies showed that the cell surface distribution pattern of Dsc3 but not Dsg3 was altered, suggesting that suprabasal acantholytic blisters were induced by IgG anti-Dsc3 antibodies rather than IgG anti-Dsg3 antibodies. Our case suggests that anti-Dsc3 antibodies may be pathogenic in cases positive for the dual cadherin autoantibodies.