Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal m...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.886226/full |
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| author | Xue Wang Xue Wang Xue Wang Xue Wang Rui Wang Rui Wang Rui Wang Dingfang Bu Leyi Wang Leyi Wang Leyi Wang Yuexin Zhang Yuexin Zhang Yuexin Zhang Yuan Chang Yuan Chang Yuan Chang Chenyang Zhang Chenyang Zhang Xixue Chen Xixue Chen Xixue Chen Xuejun Zhu Xuejun Zhu Xuejun Zhu Zhi Liu Mingyue Wang Mingyue Wang Mingyue Wang |
| author_facet | Xue Wang Xue Wang Xue Wang Xue Wang Rui Wang Rui Wang Rui Wang Dingfang Bu Leyi Wang Leyi Wang Leyi Wang Yuexin Zhang Yuexin Zhang Yuexin Zhang Yuan Chang Yuan Chang Yuan Chang Chenyang Zhang Chenyang Zhang Xixue Chen Xixue Chen Xixue Chen Xuejun Zhu Xuejun Zhu Xuejun Zhu Zhi Liu Mingyue Wang Mingyue Wang Mingyue Wang |
| author_sort | Xue Wang |
| collection | DOAJ |
| description | Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP. |
| first_indexed | 2024-12-10T16:41:00Z |
| format | Article |
| id | doaj.art-251e0f7f677e4879b53068dcac3d0169 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T16:41:00Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-251e0f7f677e4879b53068dcac3d01692022-12-22T01:41:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.886226886226Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In VivoXue Wang0Xue Wang1Xue Wang2Xue Wang3Rui Wang4Rui Wang5Rui Wang6Dingfang Bu7Leyi Wang8Leyi Wang9Leyi Wang10Yuexin Zhang11Yuexin Zhang12Yuexin Zhang13Yuan Chang14Yuan Chang15Yuan Chang16Chenyang Zhang17Chenyang Zhang18Xixue Chen19Xixue Chen20Xixue Chen21Xuejun Zhu22Xuejun Zhu23Xuejun Zhu24Zhi Liu25Mingyue Wang26Mingyue Wang27Mingyue Wang28Department of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaCentral Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaDepartment of Dermatology, Central Hospital, Zhengzhou University, Zhengzhou, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Dermatology, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Dermatology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaParaneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.https://www.frontiersin.org/articles/10.3389/fimmu.2022.886226/fullParaneoplastic pemphigusdesmoplakinplakindesmogleinacantholoysismouse model |
| spellingShingle | Xue Wang Xue Wang Xue Wang Xue Wang Rui Wang Rui Wang Rui Wang Dingfang Bu Leyi Wang Leyi Wang Leyi Wang Yuexin Zhang Yuexin Zhang Yuexin Zhang Yuan Chang Yuan Chang Yuan Chang Chenyang Zhang Chenyang Zhang Xixue Chen Xixue Chen Xixue Chen Xuejun Zhu Xuejun Zhu Xuejun Zhu Zhi Liu Mingyue Wang Mingyue Wang Mingyue Wang Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo Frontiers in Immunology Paraneoplastic pemphigus desmoplakin plakin desmoglein acantholoysis mouse model |
| title | Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo |
| title_full | Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo |
| title_fullStr | Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo |
| title_full_unstemmed | Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo |
| title_short | Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo |
| title_sort | paraneoplastic pemphigus autoantibodies against c terminus of desmoplakin induced acantholysis in vitro and in vivo |
| topic | Paraneoplastic pemphigus desmoplakin plakin desmoglein acantholoysis mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.886226/full |
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