Table 2.
Characteristics of studies included in bioelectrical signaling axis
| Author | Year | Target molecule | Intervention | Treatment Modality | Model | Antibody | Preventing Pathology | Measured Outcome | |
|---|---|---|---|---|---|---|---|---|---|
| Calcium, calcium channels, and calcium activated proteins | |||||||||
| Arredondo et al.125 | 2005 | Calpain I and II | MDL-28170 (10 µM), PD-150606 (50 µM), Calpastatin peptide (50 µM), MDL-28170 (10 µM) + PD-150606 (50 µM) + Calpastatin peptide (50 µM) | Cotreatment | In vitro, PTNM | PV IgG | +/- | Morphometric analysis of acantholysis in vitro and in vivo | |
| Kalantari-Dehaghi et al.126 | 2013 | Calcineurin | Cyclosporine A (0.1 μM) | Cotreatment | PTNM | PV IgG | + | Morphometric anaylsis of acantholysis | |
| Rötzer et al.72 | 2014 | Intracellular Calcium | BAPTA-AM (50 µM) | Cotreatment for 4 h | In vitro | PV IgG | + | KDA | |
| Walter et al.46 | 2019 | Intracellular Calcium | BAPTA-AM (200 µM) | Pretreatment for 4 h | In vitro | mPV IgG, mcPV IgG, PF IgG | + | KDA | |
| Schmitt et al.61 | 2021 | CRAC, PI4KA | BTP-2 (NA), GSK-F1 (NA) | Pretreatment for 1 h | In vitro, Ex vivo | mPV IgG, mcPV IgG, AK23, PF IgG | + | In vitro: KDA and keratin retraction measured by immunofluorescence microscopy. Ex vivo: Gross and microscopic evaluation of tissue. | |
| Schmitt et al.78 | 2023 | CRAC, PI4K | BTP-2 (10 µM), GSK-F1 (10 nM) | Pretreatment for 1 h | In vitro | 2G4 | - | KDA | |
| Xie et al.127 | 2023 | Calcineurin | FK506 (100 nM) | Cotreatment | In vitro | PV sera, AK23 | + | KDA, Immunofluorescence microscopy, and western blotting was performed for Dsg3 depletion | |
| PLC, IP3R and PI3K | |||||||||
| Esaki et al.128 | 1995 | PLC | U73122 (10 µM) | Pre and cotreatment | In vitro | PV IgG or sera | + | Keratin retraction measured by immunofluorescence microscopy | |
| Sánchez-Carpintero et al.99 | 2004 | PLC | U73122 (100 µg/g) | Pretreatment for 3 h | PTNM | PV IgG | + | Gross and microscopic evaluation of tissue | |
| Burmester et al.77 | 2020 | PI3Kα, PI3Kβ | A66 (0.1, 1, and 10 µM), TGX-221 (0.1, 1, and 10 µM) | In vitro: Pretreatment for 2 h then discarding supernatant. Ex vivo: Cotreatment | A66: In vitro, ex vivo. TGX-221: in vitro | In vitro: Immunophresis material from PV patient. ex vivo: PX43 scFv | A66 ( + ), TGX-221 (-) | In vitro: KDA. Ex vivo: Gross and light microscopic evaluation of blister formation. | |
| Schmitt et al.61 | 2021 | PLC, IP3R | U73122 (Cell culture: NA, HSOC: 50 µL of 4 µM), Xestospongin C (Cell culture: NA, HSOC: 50 µL of 2 µM) | Pretreatment for 1 hour | In vitro, Ex vivo | mPV IgG, mcPV IgG, AK23, PF IgG | + | In vitro: KDA and keratin retraction measured by immunofluorescence microscopy. Ex vivo: Gross and microscopic evaluation of tissue. | |
| Egu et al.130 | 2022 | PLC, IP3R | U73122 (50 µL of 4 µM), Xestospongin C (50 µL of 2 µM) | Pretreatment for 1 h | Ex vivo | PV IgG | +/- | length of desmosomes, percentage of split desmosomes, and keratin retraction was measured by electron microscopy. | |
| Hiermaier et al.129 | 2022 | PLC, IP3R | U73122 (4 µM), Xestospongin C (0.4 µM) | Pretreatment for1 hour | In vitro | PV IgG, PF IgG | + | KDA | |
| Schmitt et al.78 | 2023 | PLC, IP3R | U73122 (4 µM), Xestospongin C (2 µM) | Pretreatment for 1 h | In vitro | 2G4 | - | KDA | |
| PKC | |||||||||
| Kowalewski et al.133 | 1994 | PKC | Isoquinoline sulfonamide (H7) | - | In vitro | PV sera | + | Cell detachment assay | |
| Sánchez-Carpintero et al.99 | 2004 | PKC | Bisindolylmaleinamide (100 µg/g) | Pretreatment for 3 h | PTNM | PV IgG | + | Gross and microscopic evaluation of tissue | |
| Cirillo et al.134 | 2010 | PKC | Go6976 (5 nM) | Pretreatment for 1 h | In vitro | PV sera | + | Number of single cells were counted as the index of detachment | |
| Spindler et al.135 | 2011 | PKC, PKCα | Go6976 (PTNM: 500 nM in 50 µL, in vitro: 500 nM, ex vivo: NA), Safingol (PTNM: 40 µM in 50 µL, in vitro: 40 µM, ex vivo: NA), PKCα siRNA | PTNM: pretreatment for 2 h and Cotreatment. Invitro and ex vivo: Cotreatment | In vitro, ex vivo, PTNM. PKC siRNA only in vitro | PV IgG | Go6976 and Safingol (+), PKC siRNA (-) | PTNM: Gross and microscopic evaluation of blister formation. In vitro and ex vivo: immunofluorescence microscopy and KDA | |
| Dehner et al.136 | 2014 | PKC | Bisindolylmaleimide X hydrochloride (Bim-X, 1 µM) | Cotreatment | In vitro | PV IgG | + | KDA and keratin retraction measured by immunofluorescence microscopy | |
| Rötzer et al.72 | 2014 | PKC | Bim-X (1 µM) | Cotreatment | In vitro | PV IgG | + | KDA | |
| Walter et al.75 | 2017 | PKC | Bim-X (NA) | Pretreatment for 1 h | In vitro | AK23, mcPV IgG, mPV IgG, atPV IgG, PF IgG | + | KDA | |
| Egu et al.205 | 2019 | PKC | Bim-X (50 µL of 1 µM) | Pretreatment for 1 h | Ex vivo | PV IgG | - | Blister score and cleft length was calculated based on H&E stained sections. Evaluation of desmosomes were performed by electron microscopy | |
Treatment modalities: Pretreatment, Intervention added before antibody application. Cotreatment, Intervention added simultaneously with the antibody. Posttreatment, Intervention added after antibody application. Model: Ex vivo, human skin organ culture. In vitro, 2D cultured keratinocyte cell lines or primary cells. PTNM, Passive transfer neonatal mouse model. PTAM, Passive transfer adult mouse model. Antibodies: mPV IgG, mucosal PV IgG. mcPV IgG, mucocutaneous PV IgG. atPV IgG, Atypical PV IgG. PF IgG, pemphigus foliaceus IgG. Preventing Pathology: ( + ) effective in preventing antibody-induced pathology, (-) Ineffective in preventing antibody-induced pathology, (x) worsened antibody-induced pathology. KDA Keratinocyte dissociation assay, NA Not Available.