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Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen.
J Clin Invest. 2005 Apr; 115(4):870-8.JCI

Abstract

Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies specific to type VII collagen, a major constituent of the dermal-epidermal junction. Previous attempts to transfer the disease by injection of patient autoantibodies into mice have been unsuccessful. To study the pathogenic relevance of antibodies specific to type VII collagen in vivo, we generated and characterized rabbit antibodies specific to a murine form of this antigen and passively transferred them into adult nude, BALB/c, and C57BL/6 mice. Immune rabbit IgG bound to the lamina densa of murine skin and immunoblotted type VII collagen. Mice injected with purified IgG specific to type VII collagen, in contrast to control mice, developed subepidermal skin blisters, reproducing the human disease at the clinical, histological, electron microscopical, and immunopathological levels. Titers of rabbit IgG in the serum of mice correlated with the extent of the disease. F(ab')(2) fragments of rabbit IgG specific to type VII collagen were not pathogenic. When injected into C5-deficient mice, antibodies specific to type VII collagen failed to induce the disease, whereas C5-sufficient mice were susceptible to blister induction. This animal model for EBA should facilitate further dissection of the pathogenesis of this disease and development of new therapeutic strategies.

Authors+Show Affiliations

Department of Dermatology, University of Lübeck, Lübeck, Germany. csitaru@fastmail.fmNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15841176

Citation

Sitaru, Cassian, et al. "Induction of Dermal-epidermal Separation in Mice By Passive Transfer of Antibodies Specific to Type VII Collagen." The Journal of Clinical Investigation, vol. 115, no. 4, 2005, pp. 870-8.
Sitaru C, Mihai S, Otto C, et al. Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest. 2005;115(4):870-8.
Sitaru, C., Mihai, S., Otto, C., Chiriac, M. T., Hausser, I., Dotterweich, B., Saito, H., Rose, C., Ishiko, A., & Zillikens, D. (2005). Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. The Journal of Clinical Investigation, 115(4), 870-8.
Sitaru C, et al. Induction of Dermal-epidermal Separation in Mice By Passive Transfer of Antibodies Specific to Type VII Collagen. J Clin Invest. 2005;115(4):870-8. PubMed PMID: 15841176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. AU - Sitaru,Cassian, AU - Mihai,Sidonia, AU - Otto,Christoph, AU - Chiriac,Mircea T, AU - Hausser,Ingrid, AU - Dotterweich,Barbara, AU - Saito,Hitoshi, AU - Rose,Christian, AU - Ishiko,Akira, AU - Zillikens,Detlef, PY - 2004/02/20/received PY - 2004/12/21/accepted PY - 2005/4/21/pubmed PY - 2005/6/29/medline PY - 2005/4/21/entrez SP - 870 EP - 8 JF - The Journal of clinical investigation JO - J Clin Invest VL - 115 IS - 4 N2 - Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies specific to type VII collagen, a major constituent of the dermal-epidermal junction. Previous attempts to transfer the disease by injection of patient autoantibodies into mice have been unsuccessful. To study the pathogenic relevance of antibodies specific to type VII collagen in vivo, we generated and characterized rabbit antibodies specific to a murine form of this antigen and passively transferred them into adult nude, BALB/c, and C57BL/6 mice. Immune rabbit IgG bound to the lamina densa of murine skin and immunoblotted type VII collagen. Mice injected with purified IgG specific to type VII collagen, in contrast to control mice, developed subepidermal skin blisters, reproducing the human disease at the clinical, histological, electron microscopical, and immunopathological levels. Titers of rabbit IgG in the serum of mice correlated with the extent of the disease. F(ab')(2) fragments of rabbit IgG specific to type VII collagen were not pathogenic. When injected into C5-deficient mice, antibodies specific to type VII collagen failed to induce the disease, whereas C5-sufficient mice were susceptible to blister induction. This animal model for EBA should facilitate further dissection of the pathogenesis of this disease and development of new therapeutic strategies. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/15841176/Induction_of_dermal_epidermal_separation_in_mice_by_passive_transfer_of_antibodies_specific_to_type_VII_collagen_ L2 - https://doi.org/10.1172/JCI21386 DB - PRIME DP - Unbound Medicine ER -