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Neonatal Fc receptor deficiency protects from tissue injury in experimental epidermolysis bullosa acquisita

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Abstract

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease caused by autoantibodies against type VII collagen. The neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and thus controls serum levels of antibodies. In this study, we investigated the effects of FcRn deficiency on the levels of autoantibodies against type VII collagen and blistering in EBA. For this purpose, rabbit IgG against murine type VII collagen was injected into FcRn-deficient and wild-type (n = 10 per group) mice. Enzyme-linked immunosorbent assay levels of serum IgG against type VII collagen were significantly lower in mutant compared with wild-type mice. Analysis of serum levels of specific autoantibodies induced in FcRn-deficient and wild-type mice (n = 10 per group) by immunization with type VII collagen showed significantly lower serum levels of IgG against type VII collagen in FcRn-deficient mice compared with wild-type animals. Importantly, the extent of blistering disease after injection of IgG against type VII collagen was significantly reduced in FcRn-deficient mice compared to wild-type controls. Our data demonstrate that FcRn maintains levels of pathogenic autoantibodies and thereby promotes tissue injury in experimental EBA. Therefore, modulation of FcRn function using inhibitors may reduce pathogenic IgG levels, offering therapeutic benefit in patients with antibody-mediated diseases.

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Abbreviations

EBA:

epidermolysis bullosa acquisita

IF:

immunofluorescence

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Acknowledgements

This work was supported by the focus program “Autoimmunity” of the Medical Faculty of the University of Lübeck (project B1, to CS).

Conflict of interest statement

No conflict of interest has been declared.

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Authors and Affiliations

  1. Department of Dermatology, University of Lübeck, Lübeck, Germany

    Alina Sesarman, Florina Olaru, Detlef Zillikens & Cassian Sitaru

  2. Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany

    Ana Gabriela Sitaru

  3. Department of Dermatology, University of Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany

    Cassian Sitaru

Authors
  1. Alina Sesarman
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  2. Ana Gabriela Sitaru
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  3. Florina Olaru
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  4. Detlef Zillikens
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  5. Cassian Sitaru
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Corresponding author

Correspondence to Cassian Sitaru.

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Supplementary Fig. 1

Recombinant His-mCVII. Equimolar amounts of GST (lane 1), GST-mCVIIc (lane 2), DHFR-His-BP180 (lane 3), and His-mCVIIc (lane 4) were separated by 15% SDS-PAGE and stained with Coomassie blue. Immunoblot analysis with an antibody raised against murine type VII collagen, preadsorbed against GST, does not reveal reactivity against GST (lane 5) or DHFR-His-BP180 (lane 7) but detects binding to GST-mCVIIc (lane 6) and His-mCVIIc (lane 8). An RGS-His antibody (Qiagen) does not bind to GST (lane 9) and GST-mCVIIc (lane 10) but recognizes DHFR-His-BP180 (lane 11) and His-mCVIIc (lane 12) by immunoblot analysis (JPG 252 kb)

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Sesarman, A., Sitaru, A.G., Olaru, F. et al. Neonatal Fc receptor deficiency protects from tissue injury in experimental epidermolysis bullosa acquisita. J Mol Med 86, 951–959 (2008). https://doi.org/10.1007/s00109-008-0366-7

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  • DOI: https://doi.org/10.1007/s00109-008-0366-7

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