PDF(Pubmed)
Abstract：
UNASSIGNED: IgA nephropathy\'s (IgAN\'s) MEST-C classification relationship with complement activation is still not fully understood because of limited and conflicting evidence. Our study aimed to delineate this relationship through a systematic review.
UNASSIGNED: We adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines and conducted a systematic review, utilizing databases like MEDLINE (PubMed), Embase, Scopus, and Cochrane from January 2016 (year of updated MEST-C classification) to January 2023. We specifically selected studies that employed established methods to evaluate complement activation and the MEST-C classification.
UNASSIGNED: A total of 34 studies with 10,082 patients were included. Among these, 7 studies focused on the pediatric population (500 patients), and 22 studies involved 8128 patients from Asian populations. C4d, C3, C5b9, MBL, C4, and factor H-related protein 5 (FHR5) were the most frequently studied complement proteins in relation to the MEST-C classification. Complement activation assessment was primarily conducted using immunofluorescence and immunohistochemistry on kidney biopsy specimens. All complement proteins investigated showed associations with the C1-2 class. Notably, FB, FH, MASP1/3, MASP2, C5a, and C5b9 from the alternative, lectin, and terminal pathways were uniquely present in the C1-2 class. Whereas C3, FHR5, C4, and C4d were associated with all the MEST-C classes.
UNASSIGNED: We found evidence supporting the involvement of alternative and lectin complement pathways across all MEST-C classes. All examined complement factors were associated with the C1-2 class, emphasizing the critical role of complement activation, possibly at the endothelial surface. These findings may guide the development of personalized treatment strategies targeting complement pathways in relation to the MEST-C lesions.
UNASSIGNED: We adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines and conducted a systematic review, utilizing databases like MEDLINE (PubMed), Embase, Scopus, and Cochrane from January 2016 (year of updated MEST-C classification) to January 2023. We specifically selected studies that employed established methods to evaluate complement activation and the MEST-C classification.
UNASSIGNED: A total of 34 studies with 10,082 patients were included. Among these, 7 studies focused on the pediatric population (500 patients), and 22 studies involved 8128 patients from Asian populations. C4d, C3, C5b9, MBL, C4, and factor H-related protein 5 (FHR5) were the most frequently studied complement proteins in relation to the MEST-C classification. Complement activation assessment was primarily conducted using immunofluorescence and immunohistochemistry on kidney biopsy specimens. All complement proteins investigated showed associations with the C1-2 class. Notably, FB, FH, MASP1/3, MASP2, C5a, and C5b9 from the alternative, lectin, and terminal pathways were uniquely present in the C1-2 class. Whereas C3, FHR5, C4, and C4d were associated with all the MEST-C classes.
UNASSIGNED: We found evidence supporting the involvement of alternative and lectin complement pathways across all MEST-C classes. All examined complement factors were associated with the C1-2 class, emphasizing the critical role of complement activation, possibly at the endothelial surface. These findings may guide the development of personalized treatment strategies targeting complement pathways in relation to the MEST-C lesions.
摘要：
■IgA肾病（IgAN）MEST-C分类与补体激活的关系仍未完全理解，因为证据有限且相互矛盾。我们的研究旨在通过系统评价来描述这种关系。
■我们坚持系统评价和荟萃分析指南的首选报告项目，并进行了系统评价，利用MEDLINE(PubMed)等数据库，Embase,Scopus,和Cochrane从2016年1月（更新MEST-C分类的年份）到2023年1月。我们特别选择了采用既定方法评估补体激活和MEST-C分类的研究。
■共纳入34项研究，共10,082名患者。其中,7项研究集中在儿科人群（500名患者），22项研究涉及来自亚洲人群的8128名患者。C4d,C3,C5b9,MBL,C4和H因子相关蛋白5（FHR5）是与MEST-C分类相关的最常用的补体蛋白。补体激活评估主要使用免疫荧光和免疫组织化学对肾活检标本进行。所研究的所有补体蛋白均显示与C1-2类相关。值得注意的是,FB,FH,MASP1/3,MASP2,C5a,和C5b9的替代品，凝集素,和终末途径在C1-2类中独特存在。而C3、FHR5、C4和C4d与所有MEST-C类相关。
■我们发现证据支持替代和凝集素补体途径参与所有MEST-C类。所有检查的补体因子与C1-2类相关，强调补体激活的关键作用，可能在内皮表面。这些发现可以指导针对MEST-C病变的针对补体途径的个性化治疗策略的开发。
■我们坚持系统评价和荟萃分析指南的首选报告项目，并进行了系统评价，利用MEDLINE(PubMed)等数据库，Embase,Scopus,和Cochrane从2016年1月（更新MEST-C分类的年份）到2023年1月。我们特别选择了采用既定方法评估补体激活和MEST-C分类的研究。
■共纳入34项研究，共10,082名患者。其中,7项研究集中在儿科人群（500名患者），22项研究涉及来自亚洲人群的8128名患者。C4d,C3,C5b9,MBL,C4和H因子相关蛋白5（FHR5）是与MEST-C分类相关的最常用的补体蛋白。补体激活评估主要使用免疫荧光和免疫组织化学对肾活检标本进行。所研究的所有补体蛋白均显示与C1-2类相关。值得注意的是,FB,FH,MASP1/3,MASP2,C5a,和C5b9的替代品，凝集素,和终末途径在C1-2类中独特存在。而C3、FHR5、C4和C4d与所有MEST-C类相关。
■我们发现证据支持替代和凝集素补体途径参与所有MEST-C类。所有检查的补体因子与C1-2类相关，强调补体激活的关键作用，可能在内皮表面。这些发现可以指导针对MEST-C病变的针对补体途径的个性化治疗策略的开发。
