Table 4.
Characteristics of other studies
| Author | Year | Target molecule | Intervention | Treatment Modality | Model | Antibody | Preventing Pathology | Measured Outcome |
|---|---|---|---|---|---|---|---|---|
| Michel et al.212 | 1977 | Complement (C3) | Complement inactivation by heating the serum at 56 °C for 30 min or dialysis | - | Ex vivo | PV sera | - | dIF and H&E staining light microscopy examination of blister formation and acantholysis |
| Farb et al.213 | 1978 | Serine proteases, Broad spectrum proteinase | Soybean trypsin inhibitor (100 µg/mL), α2-macroglobulin (0.5 µg/mL) | Pretreatment for 24 h | In vitro | PV sera (Heat inactivated) | + | Cell detachment assay. Binding of antibodies was measured by dIF. Cellular viability was measured by incorporation of radioactive amino acid into TCA precipitable protein |
| Schiltz et al.164 | 1979 | Serine proteases, unknown | Soybean trypsin inhibitor (100 µg/mL), Thioglucose salt of gold (10 µM) | Pretreatment | Ex vivo | PV IgG | - | dIF and H&E staining light microscopy examination of acantholysis |
| Schiltz et al.171 | 1980 | C3, Protein synthesis | Complement inactivation by heating the serum at 56 °C for 1 h, Puromycin (0.1–100 µM) | Pretreatment | Ex vivo | PV IgG | C3 (-), Puromycin (+) | H&E staining light microscopy examination of acantholysis |
| Singer et al.214 | 1980 | Serine proteases, Broad spectrum proteinase | Soybean trypsin inhibitor (100 µg/mL), α2-macroglobulin (0.5 mg/mL) | Pretreatment | In vitro: Soybean trypsin inhibitor, alpha2-macroglobulin. PTNM: Soybean trypsin inhibitor | PV sera | + | Cell detachment assay |
| Morioka et al.215 | 1981 | Serine proteases, Aspartyl proteases, Cysteine peptidase | Soybean trypsin inhibitor (75–5000 µg/mL), Pepstatin A (2–40 µg/mL), N-ethylmaleimide (NEM, 0.1–1 mM) | Pretreatment | Ex vivo | PV IgG | + | dIF and H&E staining light microscopy examination of blister formation and acantholysis |
| Hashimoto et al.216 | 1983 | Plasmin, Trypsin, Serine proteases | Plasminogen (200 µg/mL), Lima bean trypsin inhibitor (NA), Aprotinin (60 TIU) | Cotreatment | Ex vivo | PV IgG, PV IgG + Plasminogen | + | H&E staining light microscopy examination of blister formation and acantholysis |
| Woo et al.217 | 1983 |
Serine proteases, Aspartyl proteases, Trypsin, Protease |
Soybean trypsin inhibitor (100 µg/mL), Aprotinin (800 units/mL), Pepstatin (50 µg/mL), Lima bean trypsin inhibitor (400 µg/mL), α2-macroglobulin (540 µg/mL), Chymostatin (600 µg/mL), Leupeptin (500 µg/mL), Antipain (100 µg/mL) | Cotreatment | In vitro | PV IgG | Soybean trypsin inhibitor, Aprotinin, α2-macroglobulin, Pepstatin, Lima bean trypsin inhibitor (+), Chymostatin, Leupeptin, Antipain (-) | Cell detachment assay |
| Kawana et al.172 | 1985 | Complement, C1q, Plasmin | Complement addition (10% normal human serum), Complement depletion, C1q depleted fraction, complement inactivation by heating the serum at 56 °C for 30 min, Plasminogen depleted serum | - | In vitro | PV IgG | Complement addition, Plasminogen depleted serum (-), Complement depletion, C1q depleted fraction, complement inactivation by heating the serum at 56 °C for 30 min (+) | Cell detachment assay |
| Anhalt et al.173 | 1986 | C5, C3 | C5 knockout, Cobra Venom Factor (CoVF) (NA) | Pretreatment | PTNM | PV IgG | C5 knockout (-), CoVF (+) | The clinical extent scoring and H&E staining light microscopy evaluation of blister formation and acantholysis |
| Naito et al.166 | 1989 | Proteases, Serine Proteases | FOY (Gabexate mesylate, ex vivo: 1–10 mg/mL, PTNM: 133 µg/g), FOY-305 (Camostat mesylate, Ex vivo: 0.5–5 mg/mL, PTNM: 100 µg/g), FUT-175 (Nafamostat Mesilate, ex vivo: 0.1–5 mg/mL, PTNM: 13 µg/g), α1-proteinase inhibitor (Ex vivo: 2.5, 25 mg/mL, PTNM: 1.67 µg/g) | Cotreatment | Ex vivo, PTNM | PV IgG | Ex vivo: all (+). PTNM: FOY-305 and α1-proteinase inhibitor (+), FUT-175 and FOY (-) | Ex vivo: H&E staining and microscopic evaluation for acantholysis. PTNM: Visual examination for Nikolsky sign as well as histological examination of acantholysis |
| Kawana et al.218 | 1990 | Ultraviolet light | UVB (0.06 to 0.18 J/cm2) | - | In vivo PV patient skin | In vivo PV patient skin | - | H&E staining light microscopy and immunofluorescence examination |
| Dobrev et al.219 | 1996 | Proteases | p-aminomethylbenzoic acid (PAMBA, 1 mg/mL), Aprotinin (10 ATrE/ml) | Cotreatment | Ex vivo | PV sera | + | H&E staining light microscopy examination of blister formation and acantholysis |
| Feliciani et al.140 | 1999 | C3 | Anti-C3 antibody (10 µg/mL) | Pretreatment for 30 min and Cotreatment | In vitro | PV sera | + | Acantholysis was measured at cell detachment assay |
| Asano et al.121 | 2001 | Proteases | PAMBA (10, 50 µg/mL), Aprotinin (0.1, 1 TIU) | Pretreatment for 30 min | In vitro | PV IgG | - | Immunofluorescence examination of keratin retraction and desmoplakin |
| Sánchez-Carpintero et al.99 | 2004 | Tyrosine kinases | Genistein (500 µg/g), Herbimycin (15 µg/g) | Pretreatment for 3 h | PTNM | PV IgG | + | Gross and microscopic evaluation of acantholysis and blister formation |
| Feliciani et al.220 | 2007 | Unknown | Tannic acid (0.1 nM) | Cotreatment | In vitro | PV IgG | x | Acantholysis was measured by cell detachment assay |
| Cirillo et al.221 | 2008 | Kinases | Staurosporine (100 nM) | Pretreatment for 1 h | In vitro | PV sera | + | Acantholysis measured by immunofluorescence microscopy |
| Delva et al.113 | 2008 | Tyrosine kinases | Genistein (40 µM) | Pretreatment for 1 h | In vitro | PV IgG | + | KDA, immunofluorescence imaging, and Dsg3 internalization assay |
| Marquina et al.145 | 2008 | Tyrosine kinases | Genistein (500 µg/g) | Pretreatment for 2 h | PTNM | PV IgG | + | Clinical activitiy and microscopic evaluation of acantholysis |
| Saito et al.68 | 2012 | Tyrosine kinases | Genistein (Ex vivo: 6.25 µg, in vitro: 50 µM) | Ex vivo: Pretreatment for 2 h. In vitro: Pretreatment for 1 h | Ex vivo, in vitro | PV IgG, AK23 | + | In vitro: KDA. Ex vivo: Gross and microscopic evaluation of blister formation. |
| Kalantari-Dehaghi et al.126 | 2013 | Mitochondria, NAD | Minocycline (0.05 mM), Nicotinamide (10 mM) | Cotreatment | PTNM | PV IgG | Minocycline (+), Nicotinamide (-) | Morphometric analysis of acantholysis |
| Liang et al.222 | 2017 | Unknown | Naringenin (50, 100, 200 µM) | 24 h after PV sera treatment | In vitro | PV sera | + | KDA |
| Wei et al.223 | 2021 | Thioredoxin-2 (Trx2) | Trx2 Overexpression | - | PTNM | PV sera | + | Gross and microscopic evaluation of acantholysis and blister formation |
Treatment modalities: Pretreatment, Intervention added before antibody application. Cotreatment, Intervention added simultaneously with the antibody. Model: Ex vivo, human skin organ culture. In vitro, 2D cultured keratinocyte cell lines or primary cells. PTNM, Passive transfer neonatal mouse model. Antibodies: PV IgG or sera, pemphigus vulgaris IgG/sera. 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.