Active Heymann nephritis in complement component C6 deficient rats

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Active Heymann nephritis (AHN) is an autoimmune kidney disease causing proteinuria.
• The role of the membrane attack complex (MAC), specifically C5b-9, in AHN pathogenesis was previously unclear.
• Data suggested MAC involvement, similar to passive Heymann nephritis.

Purpose of the Study:

• To investigate the role of the membrane attack complex (MAC) in the development of renal injury and proteinuria in active Heymann nephritis (AHN).
• To determine if complement deficiency impacts the progression of AHN.
• To explore the relationship between immune deposit size and proteinuria levels.

Main Methods:

• Induced AHN in complement component C6-deficient rats (unable to form MAC) and normal rats.
• Monitored autoantibody titers, proteinuria, and performed renal biopsies with immunofluorescence and electron microscopy.
• Assessed the effect of exogenous complement administration in deficient rats.

Main Results:

• Both C6-deficient and normal rats developed comparable high titers of anti-Fx1A autoantibodies and similar proteinuria.
• Renal biopsy findings, including Ig and C3 deposits and subepithelial electron-dense deposits, were identical between groups.
• No significant difference in disease progression or severity was observed between complement-deficient and normal rats.
• A strong positive correlation (r=0.94) was found between the size of subepithelial immune deposits and the level of proteinuria.

Conclusions:

• The membrane attack complex (MAC) does not play a major role in the pathogenesis of active Heymann nephritis (AHN).
• The growth and size of immune deposits are strongly associated with proteinuria.
• Secondary mechanisms, triggered by the expansion of immune deposits, likely damage glomerular permselectivity in AHN.