Mesangial IgA2 deposits and lectin pathway-mediated complement activation in IgA glomerulonephritis

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• Complement activation is crucial in kidney diseases, with three known pathways: classical, alternative, and lectin.
• Immunoglobulin A (IgA) glomerulonephritis (GN) is a primary glomerular disease, but the specific complement pathways and IgA subclasses involved remain unclear.

Purpose of the Study:

• To immunohistologically determine which complement pathway is activated in IgA GN.
• To identify the specific IgA subclass associated with complement activation in IgA GN.

Main Methods:

• Renal biopsy specimens from 36 IgA GN patients, 10 SLE patients, and 16 other GN patients were analyzed.
• Immunohistochemical staining used antibodies for IgG, IgA (subclasses IgA1, IgA2), IgM, complement components (C1q, C3c, C4), mannose-binding lectin (MBL), and MBL-associated serine protease-1 (MASP-1).

Main Results:

• In IgA GN patients with both IgA1 and IgA2 mesangial deposits (19/36), C3c, C4, MBL, and MASP-1 were also detected, with IgA2, MBL, and MASP-1 colocalizing.
• In IgA GN patients with IgA1 deposits only (17/36), 12 showed C3c deposition without C4, MBL, or MASP-1, indicating alternative pathway activation.
• No C1q deposition was observed in IgA GN; MBL/MASP-1 deposition occurred in SLE patients without IgA2.

Conclusions:

• Alternative pathway activation is linked to IgA1 deposits in IgA GN.
• Both alternative and lectin pathways are involved when both IgA1 and IgA2 deposits are present.
• This study is the first to report IgA2 mesangial deposits potentially activating the lectin pathway in IgA GN.