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Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease.
J Pathol. 2012 Sep; 228(1):1-7.JP

Abstract

Autoimmune bullous diseases (ABDs) are organ-specific autoimmune diseases, in which blisters on the skin and mucous membranes develop through binding of pathogenic autoantibodies to target antigens. There are two major ABD groups: the pemphigus group, showing autoantibodies to desmosomal components; and the subepidermal ABD group, showing autoantibodies to hemidesmosomal components in the epidermal basement membrane zone. Recent immunological, biochemical and molecular biological studies revealed many new autoantigens, including desmocollins, various plakin family proteins and integrins. A revised ABD classification includes new disease entities such as paraneoplastic pemphigus, IgA pemphigus and anti-laminin γ1 pemphigoid. In addition to systemic corticosteroids and various immunosuppressive agents, various adjuvant therapies for ABDs have developed. Among them, intravenous immunoglobulin (IVIG) is a promising therapy, although the therapeutic mechanisms are still unknown. Various disease models for ABDs have developed, particularly for pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita (EBA), and these have provided insights into the pathogenesis of various ADBs that suggest possible new treatment strategies. However, the fundamental mechanisms in disruption of immune-tolerance are still unknown. EBA shows autoimmunity to type VII collagen, the major component of anchoring fibrils, and EBA pathogenesis has been studied in various disease models. Previous studies suggested that, following binding of autoantibodies to type VII collagen, activation of complement, cytokine release, neutrophil migration, Fcγ receptors (FcgRs) and metalloproteinases play important roles in induction of subepidermal blisters. In this issue of the Journal of Pathology, Kasperkiewicz and colleagues reveal important roles of activating FcgRIV and inhibitory FcgRIIB in EBA pathogenesis that were recognized by conducting elegant studies using both genetic analysis and functional animal model methods. The expression equilibrium of the activating and inhibitory FcgRs can be modulated towards the inhibitory FcgRIIB by IVIG therapy, resulting in beneficial clinical effects of IVIG in EBA and other autoimmune skin-blistering diseases.

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Authors+Show Affiliations

Hashimoto T
Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan. hashimot@med.kurume-u.ac.jp
Ishii N
No affiliation info available
Ohata C
No affiliation info available
Furumura M
No affiliation info available

MeSH

AnimalsAutoantibodiesAutoantigensAutoimmune DiseasesBlisterCollagen Type VIIDisease Models, AnimalEpidermolysis Bullosa AcquisitaHumansImmune ToleranceImmunoglobulins, IntravenousImmunosuppressive AgentsMiceMice, KnockoutOrgan SpecificityReceptors, IgGSkin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22692770

Citation

Hashimoto, Takashi, et al. "Pathogenesis of Epidermolysis Bullosa Acquisita, an Autoimmune Subepidermal Bullous Disease." The Journal of Pathology, vol. 228, no. 1, 2012, pp. 1-7.
Hashimoto T, Ishii N, Ohata C, et al. Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease. J Pathol. 2012;228(1):1-7.
Hashimoto, T., Ishii, N., Ohata, C., & Furumura, M. (2012). Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease. The Journal of Pathology, 228(1), 1-7. https://doi.org/10.1002/path.4062
Hashimoto T, et al. Pathogenesis of Epidermolysis Bullosa Acquisita, an Autoimmune Subepidermal Bullous Disease. J Pathol. 2012;228(1):1-7. PubMed PMID: 22692770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease. AU - Hashimoto,Takashi, AU - Ishii,Norito, AU - Ohata,Chika, AU - Furumura,Minao, Y1 - 2012/07/26/ PY - 2011/03/13/received PY - 2012/05/08/revised PY - 2012/05/28/accepted PY - 2012/6/14/entrez PY - 2012/6/14/pubmed PY - 2012/10/10/medline SP - 1 EP - 7 JF - The Journal of pathology JO - J Pathol VL - 228 IS - 1 N2 - Autoimmune bullous diseases (ABDs) are organ-specific autoimmune diseases, in which blisters on the skin and mucous membranes develop through binding of pathogenic autoantibodies to target antigens. There are two major ABD groups: the pemphigus group, showing autoantibodies to desmosomal components; and the subepidermal ABD group, showing autoantibodies to hemidesmosomal components in the epidermal basement membrane zone. Recent immunological, biochemical and molecular biological studies revealed many new autoantigens, including desmocollins, various plakin family proteins and integrins. A revised ABD classification includes new disease entities such as paraneoplastic pemphigus, IgA pemphigus and anti-laminin γ1 pemphigoid. In addition to systemic corticosteroids and various immunosuppressive agents, various adjuvant therapies for ABDs have developed. Among them, intravenous immunoglobulin (IVIG) is a promising therapy, although the therapeutic mechanisms are still unknown. Various disease models for ABDs have developed, particularly for pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita (EBA), and these have provided insights into the pathogenesis of various ADBs that suggest possible new treatment strategies. However, the fundamental mechanisms in disruption of immune-tolerance are still unknown. EBA shows autoimmunity to type VII collagen, the major component of anchoring fibrils, and EBA pathogenesis has been studied in various disease models. Previous studies suggested that, following binding of autoantibodies to type VII collagen, activation of complement, cytokine release, neutrophil migration, Fcγ receptors (FcgRs) and metalloproteinases play important roles in induction of subepidermal blisters. In this issue of the Journal of Pathology, Kasperkiewicz and colleagues reveal important roles of activating FcgRIV and inhibitory FcgRIIB in EBA pathogenesis that were recognized by conducting elegant studies using both genetic analysis and functional animal model methods. The expression equilibrium of the activating and inhibitory FcgRs can be modulated towards the inhibitory FcgRIIB by IVIG therapy, resulting in beneficial clinical effects of IVIG in EBA and other autoimmune skin-blistering diseases. SN - 1096-9896 UR - https://www.unboundmedicine.com/medline/citation/22692770/Pathogenesis_of_epidermolysis_bullosa_acquisita_an_autoimmune_subepidermal_bullous_disease_ L2 - https://doi.org/10.1002/path.4062 DB - PRIME DP - Unbound Medicine ER -