Huda Sanna, Chau Bethany, Chen Chuanqi, Somal Herman, Chowdhury Neiloy, Cirillo Nicola
Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia.
Biology (Basel). 2022 Feb 16;11(2):314. doi: 10.3390/biology11020314.
Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The exact pathogenesis of blister formation is unknown and this has hampered the development of non-steroidal, mechanism-based treatments for this autoimmune disease. This systematic review aims to investigate the role of caspases in the pathogenesis of PV to inform the choice of more targeted therapeutic agents.
A systematic search of MEDLINE/PubMed and Scopus databases was conducted to identify eligible studies. Multiple phases of inclusion and exclusion of the primary articles were conducted in pairs, and studies were recorded and analysed according to the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Risk of bias assessment was conducted for extracted in vivo animal intervention studies using SYRCLE's risk of bias tool.
Eight articles from a total of 2338 in vitro, in vivo, and human studies met the inclusion criteria, with a high degree of inter-rater reliability. By and large, the results show that caspase activation was pathogenic in experimental PV because pan-caspase inhibitors could block or reduce PV acantholysis and blistering in vitro and in vivo, respectively. The pathogenic pathways identified involved caspase-1 and caspase-3. One study failed to show any improvement in the PV model with a caspase inhibitor. The majority of animal studies had high or unclear risk of bias.
There are consistent data pointing towards a pathogenic role of caspase activation in PV acantholysis. However, high-quality evidence to confirm that caspase inhibition can prevent PV-induced blistering in vivo is limited. Therefore, further research is required to test the preclinical efficacy of caspase inhibitors in PV.
寻常型天疱疮（PV）是一种由IgG介导的自身免疫性疾病，其特征为上皮细胞间分离（棘层松解），导致黏膜皮肤水疱形成。水疱形成的确切发病机制尚不清楚，这阻碍了针对这种自身免疫性疾病的非甾体类、基于机制的治疗方法的开发。本系统评价旨在研究半胱天冬酶在PV发病机制中的作用，为选择更具针对性的治疗药物提供依据。
对MEDLINE/PubMed和Scopus数据库进行系统检索，以确定符合条件的研究。对纳入和排除初级文章进行多阶段的配对操作，并根据系统评价和Meta分析的首选报告项目（PRISMA）的最新版本对研究进行记录和分析。使用SYRCLE的偏倚风险工具对提取的体内动物干预研究进行偏倚风险评估。
在总共2338项体外、体内和人体研究中，有8篇文章符合纳入标准，评分者间信度较高。总体而言，结果表明半胱天冬酶激活在实验性PV中具有致病性，因为泛半胱天冬酶抑制剂可分别在体外和体内阻断或减少PV棘层松解和水疱形成。确定的致病途径涉及半胱天冬酶-1和半胱天冬酶-3。一项研究未能显示半胱天冬酶抑制剂在PV模型中有任何改善。大多数动物研究的偏倚风险较高或不明确。
有一致的数据表明半胱天冬酶激活在PV棘层松解中具有致病作用。然而，证实半胱天冬酶抑制可预防PV在体内引起水疱形成的高质量证据有限。因此，需要进一步研究来测试半胱天冬酶抑制剂在PV中的临床前疗效。
