Table 3.
Characteristics of studies included in biochemical signaling axis
| Author | Year | Target molecule | Intervention | Treatment Modality | Model | Antibody | Preventing Pathology | Measured Outcome |
|---|---|---|---|---|---|---|---|---|
| Receptor tyrosine kinase growth factor receptors and signaling | ||||||||
| Hunziker et al.139 | 1986 | PDGF | Stimulated or sonicated platelets (100 µL/mL) | Cotreatment | Ex vivo | PV sera | - | H&E staining light microscopy examination of blister formation and acantholysis |
| Frušić-Zlotkin et al.43 | 2006 | EGFR | AG1478 (10 µM) | Cotreatment | In vitro | PV IgG | + | Qualitative visualization of acanthoylsis by phase contrast microscopy |
| Heupel a et al.92 | 2009 | EGFR | GW2974 (10 µM) | Pretreatment for 2 h | In vitro | PV IgG | - | KDA and keratin or F-actin retraction measured by immunofluorescence microscopy |
| Pretel et al.86 | 2009 | EGFR | Erlotinib (100 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Clinical activity and microscopic evaluation of acantholysis |
| Gil et al.87 | 2012 | EGFR | CL-387785 (10 µg/g) | Pretreatment for 2 hours | PTNM | PV IgG | + | Gross and microscopic evaluation of blister |
| Bektas et al.69 | 2013 | EGFR | CL-387785 (10 µM), PD15330 (10 µM), BPIQ-II (10 µM), Gefitinib (5–10 µM), Erlotinib (5–10 µM), AG1478 (in vitro: 0.1–10 µM, PTNM: 4 µg) | AG1478: Pretreatment for 2 h. Other inhibitors: overnight incubation or 2 h | In vitro, PTNM | PV IgG, AK23 | + | In vitro: keratin retraction and Dsg3 internalization was visualized with immunofluorescence microscopy. Dsg3 depletion was measured by western blot. Loss of intercellular adhesion was measured by KDA. PTNM: Gross and microscopic evaluation of blister formation |
| Espana et al.88 | 2013 | EGFR | CL-387785 (10 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation |
| Sayar et al.137 | 2014 | EGFR | Erlotinib (In vitro: 0.4–4 µg/mL, PTNM: 4–100 µg/g), Lapatinib (4–45 µg/g), EGFR KO | In vitro: Pretreatment for 6 h. PTNM: Pretreatment for 4 h | In vitro, PTNM | AK23 with suboptimal dose of patient derived anti-dsg1 antibody, PV IgG | + | In vitro: KDA. PTNM: Gross and microscopic histology of skin and palate. Length of blister was quantified relative percentage to total length of section. |
| Walter et al.46 | 2019 | EGFR | Erlotinib (2.5 µM) | Pretreatment for 1 h | In vitro | mPV IgG, mcPV IgG, PF IgG | + | KDA |
| Ivars et al.91 | 2020 | EGFR | CL-387785 (10 µg/g), Cetuximab (100 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation with histological scoring |
| Burmester et al.77 | 2020 | VEGFR2 | Vandetanib (0.1, 1, and 10 µM) | In vitro: Pretreatment for 2 h then discarding supernatant. Ex vivo: Cotreatment | In vitro, ex vivo | In vitro: Immunophresis material from PV patient. ex vivo: PX43 scFv | + | In vitro: KDA. Ex vivo: Gross and light microscopic evaluation of blister formation. |
| Hariton et al.16 | 2023 | EGFR | Lapatinib (9 µg/g) | Pretreatment for 4 h and post-treatment after 4 days | PTAM | AK23 | + | Percentage of hair follicle blistering was evaluated by H&E staining |
| Egu et al.85 | 2024 | EGFR (ErbB1 and ErbB1/2), TrkA | Lapatinib (44 nM), Erlotinib (2.5 µM), siTRKA (siRNA) | Lapatinib and Erlotinib: Pretreatment for 1 h. siTRKA: Pretreatment for 24 h | Lapatinib and Erlotinib: ex vivo and in vitro. siTRKA: in vitro | Lapatinib and Erlotinib: PV IgG. siTRKA: AK23, PV IgG | + | in vitro: KDA and STED microscopy. Ex vivo: Blister scoring based on H&E staining and EM. |
| Src | ||||||||
| Chernyavsky et al.84 | 2007 | Src | PP2 (10 µM) | Pretreatment | In vitro | PV IgG | + | Cell volume and keratin aggregation were measured |
| Heupel a et al.92 | 2009 | Src | PP2 (10 µM) | Pretreatment for 2 h | In vitro | PV IgG 1–5 | - | KDA and keratin or F-actin retraction measured by immunofluorescence microscopy |
| Pretel et al.86 | 2009 | Src | PP1 (1 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Clinical activity and microscopic evaluation of acantholysis |
| Gil et al.87 | 2012 | Src | PP1 (1 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister |
| Espana et al.88 | 2013 | Src | PP1 (1 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation |
| Cirillo et al.89 | 2014 | Src | Src inhibitor-1 (1 µM) | Pretreatment | In vitro | PV IgG | + | Morphometric analysis of cell-cell detachment and KDA |
| Walter et al.75 | 2017 | Src | PP2 (NA) | Pretreatment for 1 h | In vitro | AK23, mcPV IgG, mPV IgG, atPV IgG, PF IgG | + | KDA |
| Kugelmann et al.90 | 2019 | Src | PP2 (In vitro: 10 µM, ex vivo and PTNM: 50 µL of 10 µM) | In vitro: Pretreatment for 2 h, ex vivo and PTNM: Cotreatment | PTNM, In vitro, ex vivo | PV1-4 IgG, AK23 | + | In vitro: KDA. Ex vivo and PTNM: Blister score was counted in H&E stained samples |
| Ivars et al.91 | 2020 | Src | PP1 (1 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation with histological scoring |
| Schmitt et al.78 | 2023 | Src | PP2 (10 µM) | Pretreatment for 1 h | In vitro | AK23, 2G4 | + | KDA. Dsg3 internalization, keratin retraction, and desmosome numbers were visualized using STED microscopy. |
| Caspases | ||||||||
| Wang et al.160 | 2004 | Caspase 1 | YVAD-CHO (100 nM) | Cotreatment | Ex vivo | PV IgG | + | Gross and microscopic evaluation of acantholysis |
| Arredondo et al.125 | 2005 | Caspases | Z-DCB-MK, DEVD-CHO, Z-DEVD-FMK, Z-DCB-MK + DEVD-CHO + Z-DEVD-FMK (all 10 µM) | Cotreatment | In vitro | PV IgG-1a/PV IgG-2b | + | Morphometric analysis of acantholysis |
| Pretel et al.86 | 2009 | Caspases | cpm-VAD-CHO (1.6 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | clinical activity and microscopic evaluation of acantholysis |
| Schmidt et al.149 | 2009 | Caspases | VAD-fmk (20–300 µM) | Pretreatment for 1 h | In vitro | PV IgG | - | KDA and Dsg3 Immunofluorescence staining to detect keratin retraction, and intercellular gaps |
| Pacheco-Tovar et al.157 | 2011 | Caspases | Ac-DEVD-CMK (20 mM in 50 µL) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation |
| Gil et al.87 | 2012 | Caspases | cpm-VAD-CHO (1.6 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister |
| Espana et al.88 | 2013 | Caspases | cpm-VAD-CHO (1.6 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation |
| Luyet et al.158 | 2015 | Caspase 2, Caspase 3, Caspase 8, Caspase 9, Caspase 12, Caspases | Z-DEVD-FMK (40 µM), Ac-DEVD-CMK (In vitro: 40 µM, PTNM and PTAM: 6 µg/g), Z-IETD-FMK (100 µM), Z-LEHD-FMK (50 µM), Z-ATAD-FMK (10 µM), Z-VAD-FMK (40 µM) | Pretreatment | All In vitro, Ac-DEVD-CMK: PTNM and PTAM | Ac-DEVD-CMK and Z-DEVD-FMK: PV IgG1/2, AK23, AK23/PF. Z-IETD-FMK, Z-LEHD-FMK, and Z-ATAD-FMK: PV IgG1/2, AK23. Z-VAD-FMK: AK23 | Ac-DEVD-CMK, Z-DEVD-FMK, and Z-VAD-FMK ( + ), Z-IETD-FMK, Z-LEHD-FMK, and Z-ATAD-FMK (-) | In vitro: KDA. PTNM and PTAM: Quantified hair follicle blister and length of blister |
| Hariton et al.159 | 2017 | Caspase 3 | K14 promoter-driven keratinocyte-specific caspase-3-deficient mice (casp3EKO) | - | PTAM | AK23 | + | Histological quantification of telogen hair follicle blisters |
| Eichkorn et al.161 | 2022 | Caspases + UVA | Z-VAD-FMK + UVA (NA) | Pretreatment | In vitro | AK23 | + | KDA |
| Wnt Pathway | ||||||||
| Williamson et al.25 | 2006 | c-Myc, GSK3β | c-Myc inhibitor 3 (5404711, 6 µM), MI-1 (5521700), SB216763 (2 µg/g), Lithium Chloride (200 µg/g) | Pretreatment for 2 h | PTNM | c-Myc inhibitor 3: PV IgG, AK23. SB216763: AK23 | + | Gross and microscopic evaluation of blister formation |
| Schlögl et al.81 | 2018 | Casein Kinase 1 (CK1) | D4476 (100 µM) | Pretreatment for 1 h | In vitro | PV IgG, AK23 | x | KDA and immunofluorescence microscopy |
| Hariton et al.16 | 2023 | BIO | GSK-3 (10 µg/g daily for 2 days) | Injection after 4 days of AK23 treatment | PTAM | AK23 | + | Percentage of hair follicle blistering was evaluated by H&E staining |
| Glucocorticoid and G protein-coupled receptors | ||||||||
| Schiltz et al.164 | 1979 | Glucocorticoid receptor | Hydrocortisone, Triamcinolone acetide (10 µM) | Pretreatment | Ex vivo | PV IgG | - | dIF and H&E staining light microscopy examination of acantholysis |
| Anhalt et al.165 | 1986 | Glucocorticoid receptor | Dexamethansone (10 and 20 mg/kg/day in 48 h period) | 24 h pretreatment and simultaneous with PV IgG injection | PTNM | PV IgG | - | Clinical extent scoring, and H&E staining light microscopy evaluation of blister formation and acantholysis |
| Naito et al.166 | 1989 | Glucocorticoid receptor | Dexamethansone (20 µg/g) | Pretreatment | PTNM | PV IgG | - | Visual examination for Nikolsky sign as well as histological examination of acantholysis |
| Grando et al.168 | 1993 | Acetylcholine receptor | Acetylcholine, Bethanechol, Carbachol or Methacholine (All 1 nM to 100 µM) | 1 h after addition of PV IgG | In vitro | PV IgG | + | Qualitative visualization of acanthoylsis by phase contrast microscopy. Measuring permeability of [‘H]thymidine by transwell experiment |
| Asano et al.121 | 2001 | Glucocorticoid receptor | Dexamethansone (0.1, 1 mM) | Pretreatment for 24 h | In vitro | PV IgG | - | Immunofluorescence examination of keratin retraction and desmoplakin distribution |
| Nguyen a et al.154 | 2004 | Glucocorticoid receptor | Methylprednisolone (15 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Nguyen b et al.155 | 2004 | Acetylcholine receptor, acetylcholine esterase | Carbacol (0.04 µg/g), Pyridostigmine bromide (0.1 µg/g) | Cotreatment | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Chernyavsky et al.169 | 2008 | α7 nicotinic acetylcholine receptor, Muscarinic acetylcholine receptor M1 | AR-R17779 (100 µM), Pilocarpine (50 µM) | Cotreatment | In vitro | PV IgG | + | Measuring permeability monolayer 1 hour after treatment with [3H]thymidine by transwell experiment |
| Spindler et al.170 | 2010 | ß-Adrenergic receptor, Adenylyl cyclase (cAMP)/ Phosphodiesterase-4 (cAMP), Protein Kinase A (PKA) | Isoproterenol (in vitro: 100 µM, PTNM: 10 µM), Propranolol (10 µM), Forskolin/ Rolipram (5 µM/10 µM, H89 (10 µM) | PTNM: Pretreatment for 2 h or simultaneous. in vitro: simultaneous, 24 h after PV IgG treatment with media exchange for 2 h | Isoproterenol and propranolol: In vitro and PTNM. Forskolin/Rolipram, H89: In vitro | PV IgG | Isoproterenol (+), Propranolol (-), Forskolin/ Rolipram (+), H89 (-) | PTNM: Gross and microscopic evaluation of blister formation. In vitro: immunofluorescence microscopy and KDA |
| Mao et al.167 | 2017 | Glucocorticoid receptor, STAT3 | Hydrocortisone (In vitro: 100 µg/mL, PTNM: topical cream with 5% hydrocortisone), STAT3 Inhibitor XVIII (BP-1-102, In vitro: 25 nM, PTNM: topical cream with 12.5 nM rapamycin), constitutively activated Stat3 (Stat3C) overexpression | In vitro: Pretreatment. In vivo: Topical application for 3 days before antibody treatment. | In vitro, PTNM | Hydrocortisone and STAT3C: PV IgG. STAT3 Inhibitor XVIII: PV IgG, PX43 | Hydrocortisone and STAT3 Inhibitor XVIII (+), Stat3C (-) | In vitro: KDA. PTNM: Gross and histological evaluation of blister formation |
| Sigmund et al.60 | 2023 | Phosphodiesterase 4 (cAMP) | Apremilast (In vitro: 1–100 µM, ex vivo: 50 µL of 1 µM, PTNM: 2 × 30 mg/day) | In vitro and ex vivo: Pretreatment for 1 h, PTNM: Pretreatment for 2 h | In vitro, ex vivo, PTNM | PV IgG, AK23 | + | In vitro: KDA and immunofluorescence imaging. Ex vivo: Blister length in H&E histology. PTNM: Blister length was quantified in H&E histology. |
| Xie et al.127 | 2023 | Glucocorticoid receptor, Glucocorticoid receptor + Calcineurin | Clobetasol propionate (1 µM), Clobetasol + FK506 (1 µM + 100 nM) | Cotreatment | In vitro | PV sera, AK23 | + | KDA, Immunofluorescence microscopy, and western blotting was performed for Dsg3 depletion |
| TNF-α and inflammatory mediator signaling | ||||||||
| Feliciani et al.140 | 1999 | IL1α, TNF-α | Anti-IL1α antibody (2 µg/mL), Anti-TNF-α antibody (2 µg/mL) | Pretreatment for 30 min and cotreatment | In vitro | PV sera | + | Acantholysis measured by cell detachment assay |
| Feliciani et al.141 | 2000 | IL1α, TNF-α, IL1α + TNF-α, IL1, IL1β, IL2 | Anti-IL1α antibody (2 µg/mL), anti-TNF-α antibody (2 µg/mL), anti-IL1α + anti-TNF-α antibody (2 µg/mL), Anti-IL2 antibody (2 µg/mL), ICE knockout, IL1β knockout, TNFR1R2 knockout | Pretreatment for 30 min and cotreatment | In vitro: Anti-IL1α, Anti-TNF-α, Anti-IL1α + Anti-TNF-α, Anti-IL2. PTNM: ICE knockout, IL1β knockout, TNFR1R2 knockout | PV IgG | All except anti-IL2 antibody (+), Anti-IL2 antibody (-) | In vitro: Acantholysis measured by cell detachment assay. PTNM: Gross and microscopic evaluation of acantholysis and blister formation |
| Toto et al.143 | 2000 | CD28, IL10 | CD28 knockout, IL10 knockout, IL10 (50 ng) | Pretreatment for 15–60 min | In vitro: CD28 knockout. PTNM: CD28 knockout, IL10 knockout, IL10 injection | PV sera | CD28 knockout (PTNM X, in vitro -), IL10 knockout (X), IL10 injection (+) | In vitro: Acantholysis measured by cell detachment assay. PTNM: Gross and microscopic evaluation of acantholysis and blister formation |
| Feliciani et al.122 | 2003 | IL1α, TNF-α, IL1α + TNF-α, IL2 | Anti-IL1α antibody (2 µg/mL), anti-TNF-α antibody (2 µg/mL), anti-IL1α + anti-TNF-α antibody (2 µg/mL), Anti-IL2 antibody (2 µg/mL) | Pretreatment for 30 min and cotreatment | In vitro | PV sera | All except anti-IL2 antibody (+), Anti-IL2 antibody (-) | Acantholysis measured by cell detachment assay |
| Orlov et al.146 | 2006 | Fas, TNF-α, Fas + TNF-α | Fas-L (25 ng/ml), TNF-α (25 ng/ml), Fas-L + TNF-α | Cotreatment | In vitro, EpiDermFT (3D Culture) | PV IgG1/2 | x | Quantitative analysis of morphologic changes such as cell volume, cell detachment, and acantholysis in monolayers and EpiDermFT |
| Marquina et al.145 | 2008 | iNOS, eNOS, nNOS, NOS, NF-κB | 1400 W (3 µg/g), L-N5-(1-Iminoethyl) ornitine dihydrochloride (L-NIO, 30 µg/g), S-methyl-L-thiocitruline dihdrochloride (SMTC, 50 ug/g), [N(G)-monomethyl-L-arginine (L-NMMA, 0.5 µg/g), Parthenolide (6 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | 1400 W (-), L-NIO (-), SMTC ( + ), L-NMMA (+), Parthenolide (-) | Gross and microscopic evaluation of acantholysis and blister formation |
| Schmidt et al.149 | 2009 | FLIP | FLIP-L (overexpression), FLIP-S (overexpression) | Pretreatment for 1 h | In vitro | PV IgG | - | KDA and Dsg3 Immunofluorescence staining to detect keratin retraction, and intercellular gaps |
| Schulze et al.153 | 2012 | Rag2 knockout | Rag2 | - | PTAM | AK23 | - | Histologcal examination for hair follicle and suprabasal blisters of skin and palate |
| Espana et al.88 | 2013 | nNOS | SMTC (10 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Lotti et al.147 | 2018 | FasL, Soluble FasL, Membrane bound FasL | Anti-FasL Antibody (CD178, in vitro: 1 or 15 µg/mL, PTNM: 40 µg), Soluble FasL knockout, Membrane bound FasL knockout | In vitro: Pretreatment for 1 h, PTNM: 1, 2, or 3 h after PV IgG | In vitro: Anti-FasL Antibody. PTNM: Anti-FasL antibody, Soluble FasL knockout, Membrane bound FasL knockout | PV IgG | Anti-FasL Antibody (+), Soluble FasL knockout (+), Membrane bound FasL knockout (-) | In vitro: KDA. PTNM: Gross and microscopic evaluation of acantholysis and blister formation |
| Radeva et al.150 | 2019 | ST18 | ST18 overexpression | - | In vitro | PV IgG1-2, AK23 | x | KDA |
| Assaf et al.142 | 2021 | ST18, TNF-α | ST18 overexpression, Anti-TNF-α antibody (20 µg/mL) | Cotreatment | In vitro | PV sera | TNF-α (+), ST18 overexpression (-) | KDA |
| Assaf et al.151 | 2022 | ST18 | ST18 overexpression | - | In vitro | AK23 | x | Immunofluorescence staining of membrane Dsg3 |
| Lin et al.156 | 2022 | CD4 + SOCS3 | CD4 + T-Cell SOCS3 knockdown | - | In vitro | PV IgG | x | KDA |
| Lotti et al.148 | 2023 | Soluble FasL | PC111 (Anti-solube FasL Antibody, in vitro: 0.001-10 µg/mL, ex vivo: 1, 10, 50, and 100 μg) | Treatment was applied 2 h after PV antibody treatment | In vitro, ex vivo | PV IgG, PX43 scFv | + | In vitro: KDA. Ex vivo: Microscopic evaluation of acantholysis and blister formation |
| Liang et al.144 | 2023 | IL-37, IL-37 + STAT3 | Recombinent human IL-37 (100 ng/mL), Colivelin + IL-37 (0.5 µM + 100 ng/mL) | - | In vitro wildtype and Caveolin-1 shRNA cells | Rabbit polyclonal anti-Dsg3 antibody | In vitro (+), in vitro Caveolin-1 shRNA cells (-),Colivelin + IL-37 (-) | KDA |
| Luan et al.152 | 2023 | Inflammation | Thalidomide (10–50 mg/mL) | Pretreatment for 1 h | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Fc Receptors | ||||||||
| Schiltz et al.171 | 1980 | Serum, Fc portion of antibody | IgG depletion of conditioned medium by affinity chromatography, PV IgG digestion by paparin | - | Ex vivo | From PV IgG | - | H&E staining light microscopy examination of blister formation |
| Hunziker et al.206 | 1985 | Fc receptor | IVIG (Sandoglobin, 0.3–30 mg/mL) | Pretreatment for 6 and 24 h or 1 h with PV sera | Ex vivo | PV sera | + | dIF and H&E staining light microscopy examination of blister formation and acantholysis |
| Kawana et al.172 | 1985 | Fc receptor | PV F(ab´)2 fragments | - | In vitro | From PV IgG | + | In vitro epidermal cell detachment visualization using phase microscopy and coulter counter |
| Anhalt et al.173 | 1986 | Fc receptor | PV F(ab´)2, Fab´ fragments | - | PTNM | From PV IgG | PV F(ab´)2 (-), Fab´ ( + ) | Clinical extent scoring, dIF and H&E staining light microscopy evaluation of blister formation and acantholysis |
| Mascaro Jr et al.174 | 1998 | Fc receptor | PV F(ab´)2, Fab´ fragments | - | PTNM | From PV IgG | - | dIF and H&E staining light microscopy examination of blister formation and acantholysis |
| Arredondo et al.125 | 2005 | Fc receptor | IVIG | Pretreatment for 1 h | In vitro | PV IgG-1a/PV IgG-2b | + | Morphometric analysis of acantholysis in |
| Mimouni et al.176. | 2005 | Fc Receptor | IVIG (5 mg/mouse), normal F(ab´)2 (6 mg/mouse), normal Fc portion (7 mg/mouse), recombinant Dsg3 (2 mg, premixed with PV IgG) | Cotreatment | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Cirillo et al.175 | 2007 | Serum | PV IgG-free serum (0.5 mg) | - | In vitro | From PV sera | - | KDA and immunofluorescence imaging |
| de Bruin et al.58 | 2007 | Fc Receptor | PV Fab | - | In vitro | From PV IgG | - | Keratin retraction was measured by immunofluorescence microscopy |
| Mimouni et al.177 | 2010 | Fc Receptor | PV specific anti-idiotypic antibody (30 µg/mouse), IVIG (30 and 2000 µg/mouse) | - | PTNM | Anti-Dsg 1 and 3 scFv | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Zakrzewicz et al.207 | 2022 | Neonatal Fc receptor (FcRn) | Efgartigimode (25 µg/mL) | Pretreatment for 30 min or treatment after 30 min of antibody | In vitro wildtype Fc-IHH knockout cells | hAK23, mAK23, 4B3, PV IgG | Wildtype cells (+), Fc-IHH knockout cells (-), mAK23 (-) | KDA and Dsg3 depletion by western blotting |
| Others | ||||||||
| Lanza et al.208 | 2008 | Cyclin-dependent kinase 2 | Cdk2 siRNA, Roscovitine (100 µg/g) | Pretreatment for 2 h | In vitro: Cdk2 siRNA. PTNM: Roscovitine | PV sera | + | Morphometric analysis of cell-cell detachment |
| Pretel et al.86 | 2009 | mTOR | Rapamycin (5 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Clinical activity and microscopic evaluation of acantholysis |
| Lanza et al.209 | 2011 | Perk | Perk siRNA | - | In vitro | PV sera and immunoglobulin-free sera | + | KDA |
| Gil et al.87 | 2012 | mTOR | Rapamycin (5 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of tissue |
| Espana et al.88 | 2013 | mTOR | Rapamycin (5 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of tissue |
| Mao et al.71 | 2014 | MK2 | MK2 inhibitor III (In vitro: 2.5 µg/mL, PTNM: 6.25 µg), MK2 shRNA, MK2 knockout | Pretreatment for 2 hours | In vitro: MK2 inhibitor III, MK2 shRNA. PTNM: MK2 inhibitor III, MK2 knockout | PX43 | + | In vitro: Dsg3 internalization was measured by immunofluorescence microscopy and western blotting. PTNM: Gross and microscopic evaluation of blister formation. |
| Walter et al.75 | 2017 | MEK 1/2 | U0126 (NA) | Pretreatment for 1 h | In vitro | AK23, mcPV IgG, mPV IgG, atPV IgG, PF IgG | mcPV IgG, PF IgG (+), AK23, mPV IgG, atPV IgG (-) | KDA |
| Egu et al.205 | 2019 | MEK 1/2 | U0126 (50 µL of 5 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 |
| Radeva et al.150 | 2019 | MEK 1/2 | U0126 (5 µM) | Pretreatment for 1 hour | In vitro ST18 overexpression | PV IgG, AK23 | + | KDA |
| Burmester et al.77 | 2020 | PDK1, PLK1, MEK 1 | BX-795, Rigosertib, Selumetinib (0.1, 1, and 10 µM) | In vitro: Pretreatment for 2 h then discarding supernatant. Ex vivo: Cotreatment | In vitro, ex vivo | In vitro: Immunophresis material from PV patient. ex vivo: PX43 scFv | BX-795, Selumetinib (+), Rigosertib (in vitro: +, ex vivo: -) | In vitro: KDA. Ex vivo: Gross and light microscopic evaluation of blister formation. |
| Ivars et al.91 | 2020 | ADAM10 | GI254023X (150 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Gross and microscopic evaluation of blister formation with histological scoring |
| Kugelmann et al.210 | 2022 | ADAM10, ADAM17 | GI254023X (in vitro: 20 µM, ex vivo: 50 µL of 20 µM), Tapi-1 (10 µM) | Cotreatment | In vitro, ex vivo | mPV IgG 2/3, mcPV IgG1/4, AK23 | In vitro for GI254023X: mcPV IgG1, mPV IgG 2/3, and Ak23 (+), mcPV IgG4 (-). Ex vivo for GI254023X: was tested with mcPV IgG4 only (-). Tapi-1 (-) | In vitro: KDA. Ex vivo: Blister scoring based on H&E staining was evaluated |
| Hiermaier et al.129 | 2022 | MEK 1/2 | U0126 (10 µM) | Pretreatment for 1 h | In vitro | PV IgG, PF IgG | + | KDA |
| Hariton et al.16 | 2023 | Smoothened receptor | SAG (5 µg/g daily for 2 days) | Injection after 4 days of AK23 treatment | PTAM | AK23 | x | Percentage of hair follicle blistering was evaluated by H&E staining |
| Valentino et al.211 | 2023 | miR-148a | miR-148a mimic | - | In vitro | mPV IgG | + | KDA |
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.