Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• IgA nephropathy (IgAN) classification (MEST-C) and complement activation link is unclear.
• Limited and conflicting evidence exists regarding this relationship.

Purpose of the Study:

• To systematically review the relationship between IgA nephropathy's MEST-C classification and complement activation.
• To delineate the role of complement pathways in IgAN pathogenesis.

Main Methods:

• Systematic review following PRISMA guidelines (Jan 2016-Jan 2023).
• Searched MEDLINE, Embase, Scopus, Cochrane databases.
• Included studies evaluating complement activation and MEST-C classification.

Main Results:

• 34 studies (10,082 patients) analyzed; 7 pediatric, 22 Asian populations.
• C4d, C3, C5b9, MBL, C4, FHR5 frequently studied complement proteins.
• Alternative, lectin, and terminal pathways implicated, especially in C1-2 class; C3, FHR5, C4, C4d associated with all MEST-C classes.

Conclusions:

• Alternative and lectin complement pathways are involved across all MEST-C classes.
• Complement activation is critical, potentially at the endothelial surface, particularly in C1-2 class.
• Findings may inform personalized treatments targeting complement pathways in IgAN.