Serum IgA preferentially binds to cationic polypeptides in IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Biochemistry

Background:

• Primary IgA nephropathy (IgA-GN) is characterized by IgA deposition in the kidney mesangium.
• The charge properties of serum IgA in IgA-GN and other conditions were previously uncharacterized.

Purpose of the Study:

• To investigate the charge characteristics of serum IgA in IgA-GN and compare it to other renal and systemic diseases.
• To explore the potential role of charged IgA and IgA rheumatoid factor (IgA-RF) in IgA-GN pathogenesis and recurrence.

Main Methods:

• Developed a sensitive charge-dependent assay using cationized BSA (cBSA) and poly-L-lysine coated plates.
• Assayed serum IgA charge (cBSA-IgA) and IgA rheumatoid factor (IgA-RF) levels in patients with IgA-GN, Henoch Schönlein purpura (HSP), alcoholic liver cirrhosis (ALC), membranous nephropathy (MGN), and systemic lupus erythematosus (SLE).
• Assessed cBSA-IgA and IgA-RF levels in IgA-GN patients post-kidney transplantation.

Main Results:

• Significantly elevated serum cBSA-IgA levels were found in 56% of IgA-GN patients and 40% of ALC patients, but not in HSP, MGN, or SLE.
• High IgA-RF levels were observed in 39% of IgA-GN and 25% of ALC patients.
• Increased cBSA-IgA and/or IgA-RF levels correlated with mesangial IgA deposit recurrence in transplanted kidneys of IgA-GN patients.

Conclusions:

• Serum IgA possesses anionic properties that are elevated in IgA-GN and ALC.
• Both anionic IgA and IgA-RF may play a role in the pathogenesis and recurrence of IgA nephropathy.
• The developed charge-dependent assay is a sensitive tool for detecting anionic IgA.