Comparison of Complement Pathway Activation in Autoimmune Glomerulonephritis.

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• Autoimmune glomerulonephritis (GN) involves complement activation via classical (CP), lectin (LP), and alternative pathways (AP) converging on the terminal pathway (TP).
• Simultaneous evaluation of these pathways may reveal specific activation patterns and therapeutic targets for different GN types.

Purpose of the Study:

• To simultaneously assess the activation of CP, LP, AP, and TP in various autoimmune GN diseases.
• To determine the relationship between AP and CP/LP activation and TP activation in relation to disease severity.

Main Methods:

• Followed 112 patients with FSGS, MN, IgAN, LN, and AAV.
• Measured urinary complement fragments (C3a, C5a, sC5b-9, MASP-1, MASP-2, C1q, C4a, Ba, Bb) during peak clinical activity.

Main Results:

• Urinary complement biomarkers correlated with proteinuria severity.
• TP fragments were elevated in FSGS and MN compared to IgAN, LN, and AAV.
• AP and CP/LP activation markers were independently associated with TP activation across most GN types.

Conclusions:

• Both the alternative pathway (AP) and classical/lectin pathways (CP/LP) contribute to terminal pathway (TP) activation in autoimmune GN.
• AP and CP/LP represent viable therapeutic targets for autoimmune glomerulonephritis.