Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita
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 freq...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.877958/full |
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| author | Stefan Tukaj Jagoda Mantej Krzysztof Sitko Detlef Zillikens Ralf J. Ludwig Katja Bieber Michael Kasperkiewicz |
| author_facet | Stefan Tukaj Jagoda Mantej Krzysztof Sitko Detlef Zillikens Ralf J. Ludwig Katja Bieber Michael Kasperkiewicz |
| author_sort | Stefan Tukaj |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T16:01:13Z |
| format | Article |
| id | doaj.art-e46f41fffa0c441487367c5d4a07bb2b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T16:01:13Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e46f41fffa0c441487367c5d4a07bb2b2022-12-22T02:40:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.877958877958Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa AcquisitaStefan Tukaj0Jagoda Mantej1Krzysztof Sitko2Detlef Zillikens3Ralf J. Ludwig4Katja Bieber5Michael Kasperkiewicz6Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Gdańsk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdańsk, Gdańsk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdańsk, Gdańsk, PolandDepartment of Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, GermanyLübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, GermanyLübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesStress-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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.877958/fullautoimmune bullous diseases (AIBDs)epidermolysis bullosa acquisita (EBA)heat shock proteins (Hsps)Hsp70autoantibodiesnuclear factor kappa B (NF-κB) |
| spellingShingle | Stefan Tukaj Jagoda Mantej Krzysztof Sitko Detlef Zillikens Ralf J. Ludwig Katja Bieber Michael Kasperkiewicz Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita Frontiers in Immunology autoimmune bullous diseases (AIBDs) epidermolysis bullosa acquisita (EBA) heat shock proteins (Hsps) Hsp70 autoantibodies nuclear factor kappa B (NF-κB) |
| title | Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita |
| title_full | Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita |
| title_fullStr | Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita |
| title_full_unstemmed | Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita |
| title_short | Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita |
| title_sort | pathological relevance of anti hsp70 igg autoantibodies in epidermolysis bullosa acquisita |
| topic | autoimmune bullous diseases (AIBDs) epidermolysis bullosa acquisita (EBA) heat shock proteins (Hsps) Hsp70 autoantibodies nuclear factor kappa B (NF-κB) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.877958/full |
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