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

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.877958

DOI=10.3389/fimmu.2022.877958

ISSN=1664-3224

ABSTRACT=Stress-induced heat shock protein 70 (Hsp70) is a key intra- and extracellular molecular chaperone implicated in autoimmune processes. Highly immunogenic Hsp70 can activate the immune response driving the generation of anti-Hsp70 autoantibodies that are frequently found in autoimmune disorders. We recently described the direct pathological role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen (COL7) autoantibody-mediated blistering dermatosis. Here, we determined the role of anti-Hsp70 autoantibodies in EBA. We observed that serum levels of anti-Hsp70 IgG autoantibodies were significantly elevated in EBA patients compared to healthy controls and positively correlated with serum levels of pro-inflammatory interferon gamma (IFN-). The pathophysiological relevance of anti-Hsp70 IgG autoantibodies was demonstrated in an anti-COL7 antibody transfer-induced EBA mouse model in which elevated blood levels of anti-Hsp70 IgG were recorded. In addition, anti-Hsp70 IgG-treated mice had a more intense clinical and histological disease severity, 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--associated manner.