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Experimental Dermatology Oct 2019Inherited epidermolysis bullosa (EB) is a group of heterogeneous genetic disorders characterized by skin fragility. EB comprises a large spectrum of phenotypes, ranging... (Review)
Review
Inherited epidermolysis bullosa (EB) is a group of heterogeneous genetic disorders characterized by skin fragility. EB comprises a large spectrum of phenotypes, ranging from severe cutaneous and extracutaneous involvement caused by lack of key adhesion proteins, to mild cutaneous fragility caused by subtle molecular defects. Disease-causing variants in 20 different genes account for the genetic and allelic heterogeneity of EB. Here, we discuss the development of laboratory methods that enabled these discoveries and the clinical and molecular features of some new EB entities elucidated during the past 5-6 years.
Topics: Adaptor Proteins, Signal Transducing; Dystonin; Epidermolysis Bullosa; Genetic Association Studies; High-Throughput Nucleotide Sequencing; Humans; Integrin alpha3; Molecular Diagnostic Techniques; Phenotype; Plectin; Repressor Proteins; Tetraspanin 24; Whole Genome Sequencing
PubMed: 29679399
DOI: 10.1111/exd.13668 -
Archives of Dermatology May 1986
Topics: Animals; Autoantibodies; Autoantigens; Carrier Proteins; Collagen; Cytoskeletal Proteins; Dystonin; Haplorhini; Humans; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Skin; Skin Diseases, Vesiculobullous; Collagen Type XVII
PubMed: 3085598
DOI: No ID Found -
Clinics in Dermatology 1987
Review
Topics: Antigen-Antibody Complex; Autoantigens; Carrier Proteins; Collagen; Complement System Proteins; Cytoskeletal Proteins; Dystonin; Humans; Immunoglobulins; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Skin; Skin Diseases, Vesiculobullous; Collagen Type XVII
PubMed: 3552196
DOI: 10.1016/0738-081x(87)90053-8 -
Presse Medicale (Paris, France : 1983) Oct 2010Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is...
Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180. First-line treatment is local corticosteroid therapy; if local treatment fails, general corticosteroid therapy should be administered. The prognosis is good for mother and child, except that there is a risk of preterm delivery and of moderate fetal growth restriction. Management in a specialized setting is therefore necessary. Recurrence is possible during subsequent pregnancies.
Topics: Anti-Inflammatory Agents; Autoantigens; Carrier Proteins; Cytoskeletal Proteins; Diagnosis, Differential; Dystonin; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Fluorescent Antibody Technique; Histological Techniques; Humans; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid Gestationis; Pregnancy; Pregnancy Outcome; Premature Birth; Prognosis; Recurrence; Collagen Type XVII
PubMed: 20692802
DOI: 10.1016/j.lpm.2009.09.032 -
Clinical Immunology (Orlando, Fla.) Feb 2012
Topics: Animals; Autoantibodies; Autoantigens; Basement Membrane; CD40 Antigens; CD40 Ligand; Carrier Proteins; Cytoskeletal Proteins; Disease Models, Animal; Dystonin; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Membrane Glycoproteins; Mice; Mice, Transgenic; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Collagen Type XVII
PubMed: 22217422
DOI: 10.1016/j.clim.2011.12.003 -
Trends in Cell Biology Jan 2002By connecting cytoskeletal elements to each other and to junctional complexes, the plakin family of cytolinkers plays a crucial role in orchestrating cellular... (Review)
Review
By connecting cytoskeletal elements to each other and to junctional complexes, the plakin family of cytolinkers plays a crucial role in orchestrating cellular development and maintaining tissue integrity. Plakins are built from combinations of interacting domains that bind to microfilaments, microtubules, intermediate filaments, cell-adhesion molecules and members of the armadillo family. Plakins are involved in both inherited and autoimmune diseases that affect the skin, neuronal tissue, and cardiac and skeletal muscle. Here, we describe the members of the plakin family and their interaction partners, and give examples of the cellular defects that result from their dysfunction.
Topics: Amino Acid Sequence; Animals; Autoantigens; Autoimmune Diseases; Carrier Proteins; Collagen; Cytoskeletal Proteins; Desmoplakins; Dystonin; Genetic Diseases, Inborn; Humans; Intermediate Filament Proteins; Membrane Proteins; Microfilament Proteins; Molecular Sequence Data; Nerve Tissue Proteins; Non-Fibrillar Collagens; Plakins; Plectin; Protein Precursors; Sequence Alignment; Collagen Type XVII
PubMed: 11854008
DOI: 10.1016/s0962-8924(01)02180-8 -
The Keio Journal of Medicine Jun 1986
Review
Topics: Antigens, Heterophile; Autoantibodies; Autoantigens; Carrier Proteins; Collagen; Cytoskeletal Proteins; Desmosomes; Dystonin; Epidermis; Humans; Nerve Tissue Proteins; Non-Fibrillar Collagens; Skin; Collagen Type XVII
PubMed: 3537434
DOI: 10.2302/kjm.35.69 -
Seminars in Cell & Developmental Biology Sep 2017BPAG1, also known as Dystonin or BP230, belongs to the plakin family of proteins, which has multiple cytoskeleton-binding domains. Several BPAG1 isoforms are produced by... (Review)
Review
BPAG1, also known as Dystonin or BP230, belongs to the plakin family of proteins, which has multiple cytoskeleton-binding domains. Several BPAG1 isoforms are produced by a single BPAG1 genomic locus using different promoters and exons. For example, BPAG1a, BPAG1b, and BPAG1e are predominantly expressed in the nervous system, muscle, and skin, respectively. Among BPAG1 isoforms, BPAG1e is well studied because it was first identified as an autoantigen in patients with bullous pemphigoid, an autoimmune skin disease. BPAG1e is a component of hemidesmosomes, the adhesion complexes that promote dermal-epidermal cohesion. In the nervous system, the role of BPAG1a is also well studied because disruption of BPAG1a results in a phenotype identical to that of Dystonia musculorum (dt) mutants, which show progressive motor disorder. However, the expression and function of BPAG1 in muscles is not well studied. The aim of this review is to provide an overview of and highlight some recent findings on the expression and function of BPAG1 in muscles, which can assist future studies designed to delineate the role and regulation of BPAG1 in the dt mouse phenotype and in human hereditary sensory and autonomic neuropathy type 6 (HSAN6).
Topics: Animals; Dystonin; Humans; Muscle, Skeletal; Muscle, Smooth; Myocardium
PubMed: 28736206
DOI: 10.1016/j.semcdb.2017.07.016 -
Frontiers in Immunology 2019There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are... (Review)
Review
There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.
Topics: Autoantibodies; Autoantigens; Autoimmunity; Blood Coagulation; Comorbidity; Complement Activation; Dystonin; Humans; Leukocytes; Neurodegenerative Diseases; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pinocytosis; Thrombosis; Vitamin D Deficiency; Collagen Type XVII
PubMed: 31312206
DOI: 10.3389/fimmu.2019.01506 -
Frontiers in Immunology 2019Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are occasionally reported in other autoimmune blistering diseases, BP is unique in that most BP patients develop an IgE autoantibody response. It is not known why BP patients develop self-reactive IgE and the precise role of IgE in BP pathogenesis is not fully understood. However, clinical evidence suggests an association between elevated IgE antibodies and eosinophilia in BP patients. Since eosinophils are multipotent effector cells, capable cytotoxicity and immune modulation, the putative interaction between IgE and eosinophils is a primary focus in current studies aimed at understanding the key components of disease pathogenesis. In this review, we provide an overview of BP pathogenesis, highlighting clinical and experimental evidence supporting central roles for IgE and eosinophils as independent mediators of disease and via their interaction. Additionally, therapeutics targeting IgE, the Th2 axis, or eosinophils are also discussed.
Topics: Antibodies, Monoclonal, Humanized; Autoantibodies; Cytokines; Dystonin; Eosinophilia; Eosinophils; Humans; Immunoglobulin E; Immunoglobulin G; Immunoglobulins, Intravenous; Pemphigoid, Bullous; Receptors, IgE
PubMed: 31636640
DOI: 10.3389/fimmu.2019.02331