Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita

Stefan Tukaj*, Jagoda Mantej, Krzysztof Sitko, Detlef Zillikens, Ralf J. Ludwig, Katja Bieber, Michael Kasperkiewicz

*Corresponding author for this work

Abstract

Stress-induced heat shock protein 70 (Hsp70) is a key intra- and extracellular molecular chaperone implicated in autoimmune processes. Highly immunogenic extracellular Hsp70 can activate innate and acquired (adaptive) immune responses driving the generation of anti-Hsp70 autoantibodies that are frequently observed in inflammatory/autoimmune disorders. We recently described the direct pathological role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-mediated autoimmune blistering skin disease. Here, we determined the role of anti-Hsp70 autoantibodies in EBA. We observed that circulating anti-Hsp70 IgG autoantibodies were significantly elevated in EBA patients compared to healthy individuals and positively correlated with serum levels of pro-inflammatory interferon gamma (IFN-γ). The pathophysiological relevance of anti-Hsp70 IgG autoantibodies was demonstrated in an antibody transfer-induced EBA mouse model in which elevated serum levels of anti-Hsp70 IgG were found. In addition, anti-Hsp70 IgG-treated animals had a more intense clinical and histological disease activity, as well as upregulated nuclear factor kappa B (NF-κB) activation in skin biopsies compared to isotype-treated animals. Our results suggest that autoantibodies to Hsp70 may contribute to EBA development via enhanced neutrophil infiltration to the skin and activation of the NF-κB signaling pathway in an IFN-γ-associated manner.

Original languageEnglish
Article number877958
JournalFrontiers in Immunology
Volume13
Pages (from-to)877958
ISSN1664-3224
DOIs
Publication statusPublished - 20.04.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 2.21-05 Immunology
  • 2.22-19 Dermatology
  • CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

    Sadik, C. (Speaker, Coordinator), Zillikens, D. (Speaker, Coordinator), Scheffold, A. (Principal Investigator (PI)), Schmidt, E. (Principal Investigator (PI)), Heine, G. (Principal Investigator (PI)), Manz, R. (Principal Investigator (PI)), Köhl, J. (Principal Investigator (PI)), Ludwig, R. (Principal Investigator (PI)), Peipp, M. (Principal Investigator (PI)), Hammers, M. C. (Principal Investigator (PI)), Verschoor, A. (Principal Investigator (PI)), Karsten, C. (Principal Investigator (PI)), Nimmerjahn, F. (Principal Investigator (PI)), Hutloff, A. (Principal Investigator (PI)), Ibrahim, S. (Principal Investigator (PI)), Wettschureck, N. (Principal Investigator (PI)), Bieber, K. (Principal Investigator (PI)), Schilf, P. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Hirose, M. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Baines, J. F. (Principal Investigator (PI)), Bacher, P. (Principal Investigator (PI)), Hoffmann, M. (Principal Investigator (PI)), Busch, H. S. (Principal Investigator (PI)), Höppner, M. (Principal Investigator (PI)), Becker, M. (Principal Investigator (PI)), Holtsche, M. M. (Principal Investigator (PI)), Fähnrich, A. (Principal Investigator (PI)), Szymczak, S. (Principal Investigator (PI)), Murthy, S. (Principal Investigator (PI)) & Lux, A. (Principal Investigator (PI))

    01.01.22 → …

    Project: DFG ProjectsDFG Joint Research: Collaborative Research Center/ Transregios

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