Role of complement system in patients with biopsy-proven immunoglobulin G4-related kidney disease

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Hypocomplementemia is frequently observed in immunoglobulin G4-related kidney disease (IgG4-RKD).
• The specific role of the complement system in IgG4-RKD pathogenesis remains understudied.
• IgG4-RKD is a rare renal disease characterized by IgG4-positive plasma cell infiltration.

Purpose of the Study:

• To investigate the association between complement system activation, particularly C3 levels, and the clinical and pathological features of IgG4-RKD.
• To explore the potential role of complement in the development and progression of IgG4-RKD.

Main Methods:

• Retrospective analysis of 17 patients diagnosed with IgG4-RKD based on renal biopsy findings (January 2010-January 2018).
• Patients were categorized into low-C3 (<0.8 μg/L) and normal-C3 (≥0.8 μg/L) groups.
• Comparison of clinical parameters, serological markers, and renal histopathology between the two groups.

Main Results:

• The low-C3 group exhibited lower C4 levels, higher IgG4 levels, increased rheumatoid factor positivity, and more severe storiform fibrosis compared to the normal-C3 group.
• Serum C3 levels showed a negative correlation with serum IgG4, rheumatoid factor, renal C1q deposition, storiform fibrosis, interstitial fibrosis scores, and renal IgG4+ plasma cells.
• Lower C3 levels were also associated with higher blood urea nitrogen levels at the latest follow-up.

Conclusions:

• IgG4-RKD is a rare renal entity.
• The complement system, particularly C3, appears to be involved in the pathogenesis of IgG4-RKD.
• Complement activation may correlate with disease severity and specific histopathological findings in IgG4-RKD.