Autoimmunity to desmocollin 3 in pemphigus vulgaris

Xuming Mao, Arielle R. Nagler, Sara A. Farber, Eun Jung Choi, Lauren H. Jackson, Kristin M. Leiferman, Norito Ishii, Takashi Hashimoto, Masayuki Amagai, John J. Zone, Aimee S. Payne

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed 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 demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosal-dominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P = 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence, indicating distinct cellular pathogenic effects in anti-desmocollin and antidesmoglein pemphigus, despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocollin 3, or both desmosomal cadherins.

Original languageEnglish
Pages (from-to)2724-2730
Number of pages7
JournalAmerican Journal of Pathology
Volume177
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Fingerprint

Desmocollins
Pemphigus
Autoimmunity
Desmoglein 3
Desmosomal Cadherins
Autoantigens
Keratinocytes
Epidermis
Autoantibodies
Blister
Serum
Adsorption
Fluorescent Antibody Technique
Protein Isoforms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Mao, X., Nagler, A. R., Farber, S. A., Choi, E. J., Jackson, L. H., Leiferman, K. M., ... Payne, A. S. (2010). Autoimmunity to desmocollin 3 in pemphigus vulgaris. American Journal of Pathology, 177(6), 2724-2730. https://doi.org/10.2353/ajpath.2010.100483

Autoimmunity to desmocollin 3 in pemphigus vulgaris. / Mao, Xuming; Nagler, Arielle R.; Farber, Sara A.; Choi, Eun Jung; Jackson, Lauren H.; Leiferman, Kristin M.; Ishii, Norito; Hashimoto, Takashi; Amagai, Masayuki; Zone, John J.; Payne, Aimee S.

In: American Journal of Pathology, Vol. 177, No. 6, 12.2010, p. 2724-2730.

Research output: Contribution to journalArticle

Mao, X, Nagler, AR, Farber, SA, Choi, EJ, Jackson, LH, Leiferman, KM, Ishii, N, Hashimoto, T, Amagai, M, Zone, JJ & Payne, AS 2010, 'Autoimmunity to desmocollin 3 in pemphigus vulgaris', American Journal of Pathology, vol. 177, no. 6, pp. 2724-2730. https://doi.org/10.2353/ajpath.2010.100483
Mao X, Nagler AR, Farber SA, Choi EJ, Jackson LH, Leiferman KM et al. Autoimmunity to desmocollin 3 in pemphigus vulgaris. American Journal of Pathology. 2010 Dec;177(6):2724-2730. https://doi.org/10.2353/ajpath.2010.100483
Mao, Xuming ; Nagler, Arielle R. ; Farber, Sara A. ; Choi, Eun Jung ; Jackson, Lauren H. ; Leiferman, Kristin M. ; Ishii, Norito ; Hashimoto, Takashi ; Amagai, Masayuki ; Zone, John J. ; Payne, Aimee S. / Autoimmunity to desmocollin 3 in pemphigus vulgaris. In: American Journal of Pathology. 2010 ; Vol. 177, No. 6. pp. 2724-2730.
@article{4776f5cee4d645ddaeb40cc07eb8f1d0,
title = "Autoimmunity to desmocollin 3 in pemphigus vulgaris",
abstract = "Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed 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 demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosal-dominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P = 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence, indicating distinct cellular pathogenic effects in anti-desmocollin and antidesmoglein pemphigus, despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocollin 3, or both desmosomal cadherins.",
author = "Xuming Mao and Nagler, {Arielle R.} and Farber, {Sara A.} and Choi, {Eun Jung} and Jackson, {Lauren H.} and Leiferman, {Kristin M.} and Norito Ishii and Takashi Hashimoto and Masayuki Amagai and Zone, {John J.} and Payne, {Aimee S.}",
year = "2010",
month = "12",
doi = "10.2353/ajpath.2010.100483",
language = "English",
volume = "177",
pages = "2724--2730",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Autoimmunity to desmocollin 3 in pemphigus vulgaris

AU - Mao, Xuming

AU - Nagler, Arielle R.

AU - Farber, Sara A.

AU - Choi, Eun Jung

AU - Jackson, Lauren H.

AU - Leiferman, Kristin M.

AU - Ishii, Norito

AU - Hashimoto, Takashi

AU - Amagai, Masayuki

AU - Zone, John J.

AU - Payne, Aimee S.

PY - 2010/12

Y1 - 2010/12

N2 - Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed 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 demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosal-dominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P = 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence, indicating distinct cellular pathogenic effects in anti-desmocollin and antidesmoglein pemphigus, despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocollin 3, or both desmosomal cadherins.

AB - Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed 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 demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosal-dominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P = 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence, indicating distinct cellular pathogenic effects in anti-desmocollin and antidesmoglein pemphigus, despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocollin 3, or both desmosomal cadherins.

UR - http://www.scopus.com/inward/record.url?scp=78650228127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650228127&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2010.100483

DO - 10.2353/ajpath.2010.100483

M3 - Article

C2 - 20952584

AN - SCOPUS:78650228127

VL - 177

SP - 2724

EP - 2730

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 6

ER -