C4 Nephritic Factors in C3 Glomerulopathy: A Case Series

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• C3 glomerulopathy (C3G) is a rare complement-mediated kidney disease.
• Pathophysiology involves dysregulation of the complement system in the fluid phase and kidney.
• Autoantibodies targeting C3 and C5 convertases can drive this dysregulation.

Purpose of the Study:

• To investigate the presence and role of C4 nephritic factors (C4NeFs) in patients with C3 glomerulopathy.
• To understand the impact of C4NeFs on complement convertase activity.

Main Methods:

• A case series of 168 patients with C3G was analyzed.
• Patient-purified immunoglobulin Gs were tested for C4NeFs using a modified hemolytic assay.
• C4NeFs recognize C4b2a, the C3 convertase of the classical complement pathway.

Main Results:

• C4NeFs were identified in 5 C3G patients (4 with C3 glomerulonephritis).
• C4NeFs stabilized C3 and C5 convertases in a dose-dependent manner.
• C4NeFs protected C4b2a from decay and were absent in atypical hemolytic uremic syndrome patients and healthy controls.

Conclusions:

• The presence of C4NeFs in a small percentage of C3G patients underscores the complexity of autoantibody involvement.
• Identifying autoantibodies driving complement dysregulation in C3G remains challenging.
• Further research is needed to fully elucidate the autoantibody repertoire in C3G.