Extremities of the N-terminus of envoplakin and C-terminus of its linker subdomain are major epitopes of paraneoplastic pemphigus

Wang, Xue; Chen, Tiancheng; Zhao, Jian; Yang, Peng; Chen, Xixue; Tu, Ping; Zhu, Xuejun; Li, Zhi; Wang, Mingyue

doi:10.1016/j.jdermsci.2016.06.011

Cited by 9 publications

(11 citation statements)

References 23 publications

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“…found autoantibodies in a majority of patients with PNP showed a strong reactivity with multiple recombinant proteins of envoplakin and periplakin, but few cases for the C‐terminal homologous domain of periplakin (amino acid residues 1646–1756), which was detected by IB . Another study demonstrated that envoplakin residues 1–141 and residues 1684–1784 were the main antigenic epitopes of PNP proven by ELISAs, and envoplakin (residues 213–377) might be relevant to bronchiolitis obliterans or lichen planus‐like lesions . Also, anti‐epiplakin antibodies may have a significant correlation with bronchiolitis obliterans and mortality .…”

Section: Detection Results Of Immunological Methodsmentioning

confidence: 97%

“…Biochemical tests have been used to identify various target antigens ( Table 1). We also list the diagnostic sensitivity of ELISA, IB and IP for PV, 26,27,42,43 PNP, 18,29,[44][45][46] MMP, 47,48 and LAD 49 (Table 3).…”

Section: Biochemical Testsmentioning

confidence: 99%

“…82 Another study demonstrated that envoplakin residues 1-141 and residues 1684-1784 were the main antigenic epitopes of PNP proven by ELISAs, and envoplakin (residues 213-377) might be relevant to bronchiolitis obliterans or lichen planus-like lesions. 45 Also, anti-epiplakin antibodies may have a significant correlation with bronchiolitis obliterans and mortality. 79 After p170 antigen was identified as A2ML1 (a broad-range protease inhibitor), 83 Numata et al 76 demonstrated that anti-A2ML1 antibody, which can be detected by IP with high sensitivity, was associated with early onset and absence of ocular involvement, and that its possible pathogenic role may be to decrease adhesion of normal human keratinocytes by activating plasmin via inhibition of A2ML1.…”

Section: Paraneoplastic Pemphigusmentioning

confidence: 99%

See 2 more Smart Citations

Immunological methods for the diagnosis of oral mucosal diseases

Sun

Zhong

et al. 2019

Br J Dermatol

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Section: Detection Results Of Immunological Methodsmentioning

confidence: 97%

Section: Biochemical Testsmentioning

confidence: 99%

Section: Paraneoplastic Pemphigusmentioning

confidence: 99%

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Immunological methods for the diagnosis of oral mucosal diseases

Sun

Zhong

et al. 2019

Br J Dermatol

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“…Enzyme-linked immunosorbent assays (ELISAs) for envoplakin and periplakin have been developed for PNP diagnosis (38, 40–42). A series of studies using epitope mapping showed that ELISAs using the recombinant N-terminal domain and the linker subdomain of envoplakin and the linker subdomain of periplakin exhibit 75% sensitivity and 92–99% specificity (38, 40–42). ELISA is a useful technique for detecting circulating autoantibodies in PNP, especially those against Dsgs and Dscs.…”

Section: Diagnosismentioning

confidence: 99%

Paraneoplastic Pemphigus: Paraneoplastic Autoimmune Disease of the Skin and Mucosa

Kim

2019

Front. Immunol.

172

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Paraneoplastic pemphigus (PNP) is a rare but life-threatening mucocutaneous disease mediated by paraneoplastic autoimmunity. Various neoplasms are associated with PNP. Intractable stomatitis and polymorphous cutaneous eruptions, including blisters and lichenoid dermatitis, are characteristic clinical features caused by humoral and cell-mediated autoimmune reactions. Autoreactive T cells and IgG autoantibodies against heterogeneous antigens, including plakin family proteins and desmosomal cadherins, contribute to the pathogenesis of PNP. Several mechanisms of autoimmunity may be at play in this disease on the type of neoplasm present. Diagnosis can be made based on clinical and histopathological features, the presence of anti-plakin autoantibodies, and underlying neoplasms. Immunosuppressive agents and biologics including rituximab have been used for the treatment of PNP; however, the prognosis is poor due to underlying malignancies, severe infections during immunosuppressive treatment, and bronchiolitis obliterans mediated by autoimmunity. In this review, we overview the characteristics of PNP and focus on the immunopathology and the potential pathomechanisms of this disease.

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“…In the past decades, we investigated the role of the plakin family in PNP and proved that tumor cells of Castleman disease with PNP could secrete antibodies against plakin family proteins and cause detachment of cultured keratinocytes ( 2 ). Followed by epitope-mapping, we discovered that the extremities of the N-terminus of envoplakin and the C-terminus of its linker subdomain are major epitopes of PNP ( 3 ). However, patients’ antibodies purified by these two proteins failed to cause any pathological changes in animal models.…”

Section: Introductionmentioning

confidence: 99%

Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo

Wang

et al. 2022

Front. Immunol.

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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.

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Extremities of the N-terminus of envoplakin and C-terminus of its linker subdomain are major epitopes of paraneoplastic pemphigus

Cited by 9 publications

References 23 publications

Immunological methods for the diagnosis of oral mucosal diseases

Immunological methods for the diagnosis of oral mucosal diseases

Paraneoplastic Pemphigus: Paraneoplastic Autoimmune Disease of the Skin and Mucosa

Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo

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