Cross-reactivity of Autoantibodies from Patients with Epidermolysis Bullosa Acquisita with Murine Collagen VII

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Jan 20

PMID 20084423

Citations 8

Authors

Kinga Csorba

Alina Sesarman

Eva Oswald

Vasile Feldrihan

Anja Fritsch

Takashi Hashimoto

Cassian Sitaru

Affiliations

Soon will be listed here.

Abstract

The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies.

Citing Articles

The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita.

Nemeth T, Virtic O, Sitaru C, Mocsai A J Invest Dermatol. 2017; 137(10):2131-2139.

PMID: 28576735 PMC: 5624865. DOI: 10.1016/j.jid.2017.05.017.

Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo.

Nemeth T, Futosi K, Sitaru C, Ruland J, Mocsai A Nat Commun. 2016; 7:11004.

PMID: 27032818 PMC: 4821996. DOI: 10.1038/ncomms11004.

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters.

Vorobyev A, Ujiie H, Recke A, Buijsrogge J, Jonkman M, Pas H J Invest Dermatol. 2015; 135(6):1565-1573.

PMID: 25689103 DOI: 10.1038/jid.2015.51.

The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment.

Kovacs M, Nemeth T, Jakus Z, Sitaru C, Simon E, Futosi K J Exp Med. 2014; 211(10):1993-2011.

PMID: 25225462 PMC: 4172222. DOI: 10.1084/jem.20132496.

Blister-inducing antibodies target multiple epitopes on collagen VII in mice.

Csorba K, Chiriac M, Florea F, Ghinia M, Licarete E, Rados A J Cell Mol Med. 2014; 18(9):1727-39.

PMID: 25091020 PMC: 4196649. DOI: 10.1111/jcmm.12338.

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