Caspase Inhibition as a Possible Therapeutic Strategy for Pemphigus Vulgaris: A Systematic Review of Current Evidence
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Data Selection and Collection
2.4. Quality Assessment
3. Results
3.1. Search Results
3.2. Pan-Caspase Inhibition
3.3. Caspase-1 Inhibition
3.4. Caspase-3 Inhibition
3.5. Risk of Bias Assessment
4. Discussion
4.1. Effect of Caspase Inhibition
4.2. Contradicting Findings in Current Literature
4.3. Limitations and Considerations for Future Studies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author, Year | Type of Study | PV Model with Concentration of PV Sera/PV Antibody | Details of Inhibition (Type and Concentration, if Relevant) | Outcome |
---|---|---|---|---|
Arredondo et al. [18] | IN VITRO, IN VIVO | IN VITRO: Human PV IgG from 2 patients (PVIgG1b or PVIgG-2b) (1 mg/mL) incubated in human keratinocyte monolayers IN VIVO: Mice injected (intraperitoneal) with human PV IgG from two different patients (PVIgG-1b or PVIgG-2b) (0.1 mg/g body weight) | IN VITRO: Caspase inhibitors DEVD-CHO (10 μM), Z-DEVD-FMK (10 μM), and Z-DCB-MK (100 μM), given alone or as a mixture. IN VIVO: 25 μg/g body weight MDL28170 and 10 μg/g body weight Z-DCB-MK | IN VITRO: Caspase inhibitors given alone or as a mixture, can completely inhibit acantholysis in keratinocyte monolayers treated with PVIgG-2b (p < 0.05), and caused moderate decrease of acantholysis of PVIgG-1b (p > 0.05). IN VIVO: Z-DCB-MK significantly (p < 0.05) reduced extent of acantholysis induced by PVIgG-2b by approximately 50%. |
Schmidt et al. [21] | IN VITRO | HaCaT and NHEK cell lines incubated with human PV IgG (0.15 mg/mL) | Pan-caspase inhibitor z-VAD-fmk (20 mM) | Immunostaining analysis of the HaCaT and NHEK cells incubated with PV IgG showed no improvement in cell dissociation and DSG-3 fragmentation. |
Pacheco-Tovar et al. [6] | IN VIVO | Mice injected (intraperitoneal) with human PV IgG (1 mg/g body weight) | Pan-caspase inhibitor: AC- DEVD-CMK (20 mM) | Caspase inhibitor prevents macroscopical and histological blistering, apoptosis and acantholysis (p < 0.0037). |
Pretel et al. [11] | IN VIVO | Mice injected with human PV IgG (2 mg/g bodyweight) | Pan-caspase inhibitor: cpmVAD-CHO (1.6 µg/g bodyweight) | Caspase inhibitor showed complete absence of PV lesions from histological and clinical examination. |
Gil et al. [19] | IN VIVO | Mice injected with human PV IgG (2 mg/g bodyweight) | Pan-caspase inhibitor (cpmVAD-CHO) (1.6 µg/g body weight) | Caspase inhibitor led to absence of clinical PV lesions and suprabasal acantholysis |
Author, Year | Type of Study | PV Model with Concentration of PV Sera/PV Antibody | Details of Inhibition (Type and Concentration, if Relevant) | Outcome |
---|---|---|---|---|
Wang et al. [12] | IN VITRO | HaCaT cell line and skin organ cultures incubated with human PV IgG (2.5 mg/mL) | YVAD-CHO (0–20, 100 nM) | Caspase inhibitor prevents PVIgG-induced cell death and lesion formation via histological analysis. |
Author, Year | Type of Study | PV Model with Concentration of PV Sera/PV Antibody | Details of Inhibition (with Concentrations, if Relevant) | Outcome |
---|---|---|---|---|
Hariton et al. [17] | IN VIVO | Mice injected with AK23 antibody (12.5 μg/g body weight) | Caspase-3 genetic knock-out (KO) (-/-) | The caspase-3 KO showed approximately a 50% reduction in hair follicle PV blisters (p < 0.05) and a significant decrease in pro-caspase-3 biomarkers (p < 0.05) when compared to PV wildtype and heterozygotes. |
Luyet et al. [20] | IN VIVO | Mice injected with AK23 antibody (12.5 μg/g body weight) | Caspase-3 inhibitor Ac-DEVD-CMK (6 μg/g) | The caspase-3 inhibitor showed approximately a 15% decrease in hair follicle PV blisters. |
Arredondo et al. [16] | Pacheco-Tovar et al. [6] | Hariton, W.V. [15] | Pretel et al. [9] | Gil et al. [17] | Luyet et al. [18] | Signalling Question | Type of Bias and Domain |
---|---|---|---|---|---|---|---|
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Did the investigators describe a random component in the sequence generation process? | Selection bias (sequence generation) |
Yes | Yes | Yes | Yes | Yes | Yes | Was the distribution of relevant baseline characteristics balanced for the intervention and control groups? | Selection bias (baseline characteristics) |
Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Was the timing of disease induction adequate? | Selection bias (baseline characteristics) |
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Could the investigator allocating the animals to intervention or control group not foresee assignment due to one of the following or equivalent methods? | Selection bias (allocation concealment) |
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Did the authors randomly place the cages or animals within the animal room/facility? | Performance bias (random housing) |
Yes | Yes | Yes | Yes | Yes | Yes | Is it unlikely that the outcome or the outcome measurement was influenced by not randomly housing the animals? | Performance bias (random housing) |
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Was blinding of caregivers and investigators ensured, and was it unlikely that their blinding could have been broken? | Performance bias (blinding) |
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Did the investigators randomly pick an animal during outcome assessment, or did they use a random component in the sequence generation for outcome assessment? | Detection bias (random outcome assessment) |
Unclear | No | Unclear | Unclear | Unclear | No | Was blinding of the outcome assessor ensured, and was it unlikely that blinding could have been broken? | Detection bias (blinding) |
No | No | No | No | Yes | Yes | Was the outcome assessor not blinded, but do review authors judge that the outcome is not likely to be influenced by lack of blinding? | Detection bias (blinding) |
Unclear | Yes | Yes | No | Yes | Yes | Were all animals included in the analysis? | Attrition bias (incomplete outcome) |
No | No | No | No | Yes | Unclear | Was the study protocol available and were all of the study’s pre-specified primary and secondary outcomes reported in the current manuscript? | Reporting bias (selective outcome reporting) |
Yes | Yes | Yes | Yes | No | Yes | Was the study protocol not available, but was it clear that the published report included all expected outcomes (i.e., comparing methods and results)? | Reporting bias (selective outcome reporting) |
Yes | Yes | Unclear | Yes | Unclear | No | Was the study free of contamination (pooling drugs)? | Other sources of bias |
Yes | Yes | Yes | Yes | Yes | Yes | Was the study free of inappropriate influence of funders? | Other sources of bias |
Unclear | Unclear | Unclear | Unclear | Unclear | Yes | Was the study free of unit of analysis errors? | Other sources of bias |
Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Were design-specific risks of bias absent? | Other sources of bias |
Unclear | No | No | Unclear | Unclear | No | Were new animals added to the control and experimental groups to replace drop-outs from the original population? | Other sources of bias |
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Huda, S.; Chau, B.; Chen, C.; Somal, H.; Chowdhury, N.; Cirillo, N. Caspase Inhibition as a Possible Therapeutic Strategy for Pemphigus Vulgaris: A Systematic Review of Current Evidence. Biology 2022, 11, 314. https://doi.org/10.3390/biology11020314
Huda S, Chau B, Chen C, Somal H, Chowdhury N, Cirillo N. Caspase Inhibition as a Possible Therapeutic Strategy for Pemphigus Vulgaris: A Systematic Review of Current Evidence. Biology. 2022; 11(2):314. https://doi.org/10.3390/biology11020314
Chicago/Turabian StyleHuda, Sanna, Bethany Chau, Chuanqi Chen, Herman Somal, Neiloy Chowdhury, and Nicola Cirillo. 2022. "Caspase Inhibition as a Possible Therapeutic Strategy for Pemphigus Vulgaris: A Systematic Review of Current Evidence" Biology 11, no. 2: 314. https://doi.org/10.3390/biology11020314
APA StyleHuda, S., Chau, B., Chen, C., Somal, H., Chowdhury, N., & Cirillo, N. (2022). Caspase Inhibition as a Possible Therapeutic Strategy for Pemphigus Vulgaris: A Systematic Review of Current Evidence. Biology, 11(2), 314. https://doi.org/10.3390/biology11020314